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Clinical Genetics Leaflets

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  • Predictive Testing For a Breast Cancer 1(BRCA1) Gene Alteration

    The leaflet is detailed below, or you can download the 'Predictive testing for a Breast Cancer 1(BRCA1) Gene alteration' leaflet in PDF.

    Cancer is common in the general population with 1 in 2 people being diagnosed with a cancer. Approximately 1in 8 women will be diagnosed with breast cancer and most cancer occurs just by chance. Our suspicions of an inherited explanation for the cancers in a family are raised if the same or similar cancers occur across different generations at a younger age than expected. This is why genetic testing would be offered to a family.

    What Are Genes And Chromosomes?

    Humans are made up of trillions of cells. At the centre of almost all of your cells is a ball-shaped structure called the nucleus, inside of which are 46 thread-like structures called chromosomes. Chromosomes are long strands of DNA (Deoxyribonucleic Acid). It is estimated that if a strand of DNA was stretched out, it would be around two meters long, even though the average cell is smaller than a pinhead.    

    We have 23 pairs of chromosomes; one of each pair is inherited from your mother and one of each pair from your father. Chromosomes 1-22 are arranged in size order with number 1 being the largest and 22 the smallest. The last pair of chromosomes determines if you are a male or female. Males are XY and females are XX. Chromosomes contain an estimated 20-30,000 pairs of genes that make us who we are. As we have pairs of chromosomes we therefore have pairs of genes.

    Genes are often called the blueprint for life because they tell each of your cells what to do and when to do it. For example, some genes determine how tall you will be; some what colour your hair will be; some genes are responsible for maintenance in our bodies and some for our development, and so on. Genes do this by making proteins. In fact, each gene is really just a ‘recipe’ or a code for making a certain protein. In order for a gene to do the job it is supposed to do, the ‘recipe’ or code needs to be written correctly. If the ‘recipe’ is wrong, the protein is either not made, or is made incorrectly so cannot do the job it is supposed to do. This is sometimes called a gene alteration, a spelling mistake or a gene mutation.

    What Is The Role Of The BRCA1 Gene?

    The role of the BRCA 1 gene is to protect the body against developing cancer in certain areas of the body. BRCA1 genes are called tumour suppressor genes and the protein produced from them helps prevent cells from growing and dividing too rapidly or in an uncontrolled way. The pair of BRCA1 genes is found on chromosome 17.

    What Is The Main Cancer Risks Associated With Having An Altered BRCA1 Gene?

    Associated risks

    General Population risk

    With a BRCA1 gene alteration

    Breast cancer

    ~ 12% = 1 in 8 women

    60-80% lifetime risk

    Ovarian cancer

    ~1-2% = 1 in 50-100 women

    30-60% lifetime risk

    Male breast cancer

    Very low

    0.1-1%

    Prostate cancer

    ~10%

    Thought to be slightly above population risk

    What Can Be Done To Help Manage These Risks?

    For each of the high risk cancers, screening and surgical options are discussed. Different options are available to men and women, and options can also differ dependent on what age you are.

    For Women

    Breast Screening: Women who have a BRCA1 gene alteration are offered high risk breast screening. The National Institute for Health and Care Excellence (NICE) screening recommendations are for a Magnetic Resonance Imaging (MRI) scan from the age of 30 to 49 and a yearly mammography from 40 to 69. 

    Women who opt not to be tested for the BRCA1 gene alteration, and are at 50% risk of inheriting it, are offered annual MRI scans from 30 to 49 and annual mammography from 40 to 59. These women will then join the NHS Breast Screening Programme for mammograms every three years from 60-70.

    Breast screening is not offered routinely to women over the age of 70 regardless of whether they carry a BRCA1 gene alteration or not (by 2016 this will be extended up to the age of 73). However screening can be requested from your local breast screening unit and is something we would recommend if you were a carrier of a BRCA1 gene alteration.   We also suggest that women carry out monthly self-examination of the breasts.

    Breast Surgery: Women, who have a BRCA1 gene alteration, also have the option of having surgical removal of both breasts (bilateral mastectomy). Although this procedure could significantly reduce the risk of developing breast cancer it will not remove the risk entirely. We also recognise this is a radical step that requires careful consideration. Therefore women who choose this option are fully supported throughout the process and not rushed into making any decisions.

    Ovarian Screening and Surgery: Ovarian screening involves regular blood tests approximately 3-4 times a year, to measure a marker in the blood called CA125 and also by annual ultrasound from the age of 35.

    However, ovarian screening does not reliably inform us of cancers early enough in order for them to be treated effectively.

    Therefore, for women who are BRCA1 carriers, over the age of 35 and have completed their families we would encourage those to think about having their ovaries and fallopian tubes removed (bilateral salpingo-oophorectomy). This can significantly decrease the risk of developing ovarian cancer but, again the risk of cancer is never removed entirely.

    There are clear advantages to having your ovaries and fallopian tubes removed, however they do need to be weighed with the potential disadvantage of being put into an early menopause and the possible need for HRT. The advantages and disadvantages of HRT could be further discussed with a gynaecologist if you choose to go ahead with this process.

    Chemoprevention: Recent guidelines have suggested that ladies at high risk of breast cancer be offered chemo-prevention medications. Research suggests these medications can reduce the risk of developing breast cancer however they do have significant side effects. Please ask for a leaflet outlining the risks and benefits of chemoprevention if you think this is something you might be interested in.

    For Men

    Men are not offered any breast screening, but we suggest they check their chest and armpit areas and seek medical advice for any unusual lumps. Prostate screening should be undertaken annually from the age of 40 and can be provided through the GP.

    How BRCA1 Gene Alterations Are Passed Down (Inherited) Through Families?

    The way BRCA1 gene alterations are inherited is called DOMINANT inheritance. This is caused by an alteration in only one copy of the BRCA1 gene. Even though we each have 2 copies of the BRCA1 gene the normal copy cannot compensate for the altered copy and a person with one altered BRCA1 gene has an increased risk of developing cancer.

    If a parent carries an altered BRCA1gene, each of their children has a 50%, or 1 in 2 chance of inheriting the altered gene and therefore having an increased risk of developing cancer. For each child, regardless of their sex, the risk is the same = 50%.

    What Is Predictive Testing?

    Predictive testing is offered to family members who are known to be at risk of inheriting a gene alteration that has been identified in the family but are currently well. Predictive testing is usually offered over a series of appointments to allow the opportunity to consider options and choices with time for reflection in-between. How many appointments a person requires varies considerably from person to person and is negotiated on an individual basis with your genetic counsellor team. The overall aim of the predictive testing process is to help prepare you for your results whatever they are.

    What Are The Issues To Think About When Deciding Whether Or Not To Have A Gene Test?

    A genetic test can establish whether you have an alteration in a gene which could affect your health.

    It can be difficult to make a decision about whether or not to have a genetic test. We all have gene alterations. Many of these do not affect our health. It is still quite unusual for a person to know they have an alteration in a specific gene.

    There are reasons for and against having a genetic test. Within one family, relatives often have different views. You should try to make your own decision, without feeling pressured from relatives or other influences.

    You will have plenty of opportunity to talk through the issues surrounding the test with the genetic counsellor or doctor.

    How Do You Think You Would Cope If The Test Were To Show That You Have Inherited The Altered Gene?

    For some people, knowing that they have the altered gene is preferable to living with uncertainty. Having a genetic test enables them to make decisions about the future and about screening and measures to reduce their risk. Other people may prefer not to have the test because they may feel very anxious if the test shows that they have the altered gene.

    How Do You Think You Would Cope If The Test Were To Show That You Have Not Inherited The Altered Gene?

    Perhaps surprisingly, it can often take people some time to get used to the knowledge that they do not have the altered gene. This can be particularly difficult when other relatives have a different result.

    People who do not have the altered gene have the same chance of developing cancer as other people in the general population. 

    If The Test Were To Show That You Have The Altered Gene, This Would Mean That Your Children Would Also Be At Risk Of Having The Altered Gene. How Do You Think You Might Feel About This?

    Having a genetic test may be important to other people, such as your children. It will help them to understand their own risk and if necessary make choices about screening and risk reducing options.

    It can be very difficult knowing that you could have passed on an altered gene to your children. This can be hard to deal with even if you know that you had no control over which genes you passed on

    If You Were To Have The Test, Would You Want To Tell Anyone The Test Results?

    It is important to think about who you would want to know about your test as it is very personal information. Many people who attend our clinic find that it helps to confide in a partner, trusted friend or relative.

    Would Having The Test Affect Your Ability To Get Life Or Medical Insurance?

    At present, if you have already obtained your insurance, having the test should not affect your current policies. However, it is not possible to know whether it will affect your ability to get or to change insurance policies in the future.

    Would Having The Test Affect Your Employment?

    If the test shows you have the altered gene it would be your decision whether or not to inform your present employers. Some employers might ask about this if you apply for a new job. 

    It is important that each family member makes the decision that is best for them. We will support you whether you decide to have the test or whether you decide against having the test. It is your decision!

    What Happens If I Choose To Go Ahead And Have A Test?

    - After you have the opportunity to discuss the positives and negatives of predictive testing, if you wish to have the test you will be asked to read and sign a consent form and a small blood sample will then be taken.

    - Once the blood is taken, the laboratory staff would test the sample to find out whether or not you have inherited the altered gene known in your family.

    -Test results are usually available 4-6 weeks after having your blood taken and you can choose to have your results over the phone or in a clinic appointment. 

    IF, FOR SOME REASON YOU, HAVE NOT RECIEVED YOUR RESULTS WITHIN 4-6 WEEKS AS EXPECTED PLEASE CALL THE CLINICAL GENETICS DEPARTMENT ON 0151 802 5008. Please remember to have your G number and W number handy for this call so we can quickly and correctly identify you.

    What Happens If I Choose Not To Go Ahead With Having A Test?

    -We may still recommend screening to you as explained earlier in this leaflet.

    You can change your mind and decide not to have the test at any time before the result is given.  

    Other Factors to Consider

    Insurance and Genetics

    For some types of insurance it is necessary to provide medical information, including genetic information, to the insurers in order for them to set up your policy and work out your premiums. The types of policy that require a medical history or genetic test are likely to be, life cover, critical illness insurance and income protection insurance.

    We would suggest that if yourself or family members are considering taking out new insurance policies in the future that consideration be given to the possible affect genetic test results could have on the ability to gain insurance or the premiums charged. Genetic Test results do not affect insurance policies already in place.

    The Association of British Insurers (ABI) has a Code of Practice ‘The Concordat and Moratorium on Genetic and Insurance’.

    • Insurance companies cannot ask for the Predictive Genetic Test results of individuals or family members (unless for Huntington Disease over £500,000). A Predictive Genetic Test is where an individual has a family member with a genetic condition, but who personally has no symptoms, signs or abnormal medical tests consistent with the condition at time of testing.
    • If a family member has been diagnosed with a genetic condition based on a Diagnostic Genetic Test then you or family members will need to mention this when asked to provide your family’s medical history. In many cases Diagnostic Genetic Testing is used to confirm a diagnosis when a particular condition is suspected because of symptoms, signs or abnormal non-genetic tests including unusual findings on a routine blood test or other test.

     

    Sources of Further Information Include

    The Association of British Insurers Genetics Frequently Asked Question’s https://www.abi.org.uk/products-and-issues/topics-and-issues/genetics/genetics-faqs/

    Genetic Alliance UK (Charity) Genetics & Insurance http://www.geneticalliance.org.uk/information/living-with-a-genetic-condition/insurance-and-genetic-conditions/

     

    Family planning-

    Everyone who has an inherited genetic condition can choose from a variety of options to ensure they do not pass it on. It is a highly personal decision and there is certainly no expectation that couples have to do anything to prevent passing on a BRCA1 gene alteration, but for couples who wish to consider this, some of the choices can include:

    • Preimplantation genetic diagnosis (PGD)

    PGD involves the use of assisted reproductive technology (ART)|, which is also offered to couples with fertility problems. The aim is to obtain and fertilize a number of eggs. Once fertilized, the embryos develop for six days and then a number of cells are removed from each embryo. The genetic material (DNA or chromosomes) within each cell is then tested for the genetic or chromosome abnormality. Up to two unaffected embryos are then transferred to the uterus with the hope that they will implant and form a pregnancy. If successful, the baby should not be affected by the disorder it was tested for.

    More information can be obtained http://www.pgd.org.uk

    • Adoption
    • Sperm or egg donation: dependent on who carries the gene alteration.

    Our experience is however that very few couples who carry a BRCA1 gene alteration choose any of the above options.

    Oral Contraceptives

    There have been a number of studies looking at the relationship between taking oral contraceptives and breast cancer risk but unfortunately the findings can often differ between different studies. However, overall, we know that taking the combined oral contraceptive pill (COC) increases the risk of breast cancer in all women. The risk appears to be confined to current and recent use and the risk drops once you stop taking the pill, and will return to normal after a number of years without use. It is felt that 10 years after stopping the COC, the breast cancer risk is the same as if you had never taken it at all.

    One study showed an increased risk of breast cancer under the age of 40 to women who were carriers of a BRCA1 gene alteration (Narod SA et al (2002) Oral Contraceptives and the Risk of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers, J Natl Cancer Inst 94:1773-9).

    Use of COC also reduces the risk of ovarian cancer proportionally to the duration of use but should never be prescribed for this reason only.

    There is no evidence regarding progesterone only contraceptives and breast cancer risk associated with family history.

    You should discuss the use of oral contraceptives with your GP to weigh up the risks and benefits to help you make the decision that is right for you. You may also want to look at the Cancer research UK website for further information

    Useful websites

    Genetic Alliance UK                                                               www.geneticalliance.org.uk

    Cancer research group UK (CRUK)                                      www.cruk.org.uk

    National Institute for Health Care and Excellence (NICE)     www.nice.org.uk/Guidance/CG41

     

    All images in this leaflet were provided by NHS National Genetics and Genomics Education Centre

  • Information for Men from Families with a Known Alteration in the BRCA1 Gene

    The leaflet is detailed below, or you can download the 'Information for men from families with a known alteration in the BRCA1 gene' leaflet in PDF.

    Breast Cancer

    In the UK, breast cancer affects 1 in 8 women during their lifetime (Cancer research UK July 2012). Most of these women are aged over 60. It is very rare for men to develop breast cancer.

    Ovarian Cancer

    Ovarian cancer is less common. In the UK, about 1 in 50 women are affected during their lifetime (Cancer research UK July 2012). Most of these women have been through the menopause.

    Prostate Cancer

    It has been estimated that the lifetime risk of prostate cancer is around 1 in 8 for the men in the UK (Cancer research UK July 2012). It is strongly related to age and very few men under the age of 50 will be diagnosed with prostate cancer. Around three quarters of cases occur in men over 65 years with the largest number diagnosed in those aged 70-74.

    What is Inherited Cancer?

    In some families, women over several generations develop breast or ovarian cancer. Sometimes in these families men may also have had a prostate cancer. As this cancer is fairly common, especially in men over the age of 75, it may not be linked to breast or ovarian cancers. Occasionally men in these families have had breast cancer.

    In a very small number of families some relatives may have inherited a gene alteration making them more likely to get cancer.

    What are Genes?

    Our genes are the unique set of instructions inside our bodies which makes each of us individual. There are many thousands of different genes, each carrying a different instruction. As well as determining how we look, our genes control the way each cell or building block of the body works. Specific genes control specific cell types. Some genes are particularly important in controlling the way the cells in the breasts and ovaries grow. These genes may also be important in the growth of cells in the prostate.

    We inherit two copies of each of our genes, one from our mother and one from our father.

    Why do some Genes Increase the Risk of Cancer?

    The instructions in each gene are like a code. Sometimes the code differs from that of a normal gene.

    For example imagine the normal code for a gene is:

    1-2-3-4-5-6-7-8-9-10-11-12-13-14

    The gene passed down through the family may have a slightly different code:

    1-2-3-4-5-6-7-8-9-9-10-11-12-13-14 

    This gene will give slightly different instructions to the cells it controls than a gene with a normal code. We call this an altered gene.

    If the altered gene is one that controls breast, ovarian and possibly prostate cells, there is a higher chance that breast, ovarian or prostate cancer may develop.

    How can an Altered Gene be Inherited?

    If one parent (either the mother or the father) has an altered BRCA1gene, this can be passed down to a child.

    Each child has a 50/50 chance of inheriting that parent's altered gene and a 50/50 chance of inheriting that parent's normal gene.

    Which Gene Increases the Risk of these Cancers?

    The two genes which we know are important in breast, ovarian and possibly prostate cancer when they are altered in this way are called BRCA1 and BRCA2. There may be other important genes which have not yet been discovered.1-2-5-6-7-8-9-10-11-12-131-2-3-4-5-6-7-8-9-10-11-12- 

    What if a Man Inherits an Altered BRCA1 Gene?

    If a man inherits an altered BRCA1 gene his lifetime risk of developing prostate cancer is increased above the general population. He also has a slightly increased risk of developing breast cancer.

    What Screening is Available for Men Who Carry the Altered Gene, or who are at 50/50 Risk of Having the Altered Gene?

    Although no breast screening is available to men with a BRCA 1 gene alteration, we do advise that men check their breast and armpit area for any lumps and reports any concerns to their GP.

    No screening test for prostate cancer has been shown to detect all cases of cancer and sometimes results of tests can be abnormal, even in men who do not have cancer. This can cause a great deal of anxiety as well as unnecessary investigations. However, if a man is found to be at increased risk of prostate cancer he can discuss screening with his GP who will advise him about what is available locally.

    Prostate screening involves examination of the prostate and a blood test. To examine the prostate, the doctor inserts a finger into the back passage to check that the prostate is not enlarged. The blood test measures the level of a substance called PSA (Prostate Specific Antigen) that is raised in prostate cancer.

    If you need more advice about any aspect of genetic testing for men, you are welcome to contact:

    Cheshire and Merseyside Clinical Genetics Service

    Liverpool Women’s Hospital

    Crown Street

    Liverpool, L8 7SS

    Telephone 0151 802 5001 or 5002

    Facsimile: 0151 702 4283

  • Predictive Testing For a Breast Cancer 2(BRCA2) Gene Alteration

    The leaflet is detailed below, or you can download the 'Predictive testing for a Breast Cancer 2(BRCA2) Gene alteration' leaflet in PDF.

    Cancer is common in the general population with 1 in 2 people being diagnosed with a cancer. Approximately 1in 8 women will be diagnosed with breast cancer and most cancer occurs just by chance. Our suspicions of an inherited explanation for the cancers in a family are raised if the same or similar cancers occur across different generations at a younger age than expected. This is why genetic testing would be offered to a family.

    What Are Genes And Chromosomes? 

    Humans are made up of trillions of cells. At the centre of almost all of your cells is a ball-shaped structure called the nucleus, inside of which are 46 thread-like structures called chromosomes. Chromosomes are long strands of DNA (Deoxyribonucleic Acid). It is estimated that if a strand of DNA was stretched out, it would be around two meters long, even though the average cell is smaller than a pinhead.    

     

    We have 23 pairs of chromosomes; one of each pair is inherited from your mother and one of each pair from your father. Chromosomes 1-22 are arranged in size order with number 1 being the largest and 22 the smallest. The last pair of chromosomes determines if you are a male or female. Males are XY and females are XX. Chromosomes contain an estimated 20-30,000 pairs of genes that make us who we are. As we have pairs of chromosomes we therefore have pairs of genes.

    Genes are often called the blueprint for life because they tell each of your cells what to do and when to do it. For example, some genes determine how tall you will be; some what colour your hair will be; some genes are responsible for maintenance in our bodies and some for our development, and so on. Genes do this by making proteins. In fact, each gene is really just a ‘recipe’ or a code for making a certain protein. In order for a gene to do the job it is supposed to do, the ‘recipe’ or code needs to be written correctly. If the ‘recipe’ is wrong, the protein is either not made, or is made incorrectly so cannot do the job it is supposed to do. This is sometimes called a gene alteration, a spelling mistake or a gene mutation.                                                                                   

    What Is The Role Of The BRCA2 Gene?

    The role of the BRCA 2 gene is to protect the body against developing cancer in certain areas of the body. BRCA2 genes are called tumour suppressor genes and the protein produced from them helps prevent cells from growing and dividing too rapidly or in an uncontrolled way. The pair of BRCA2 genes are found on chromosome 13.

    What Is The Main Cancer Risks Associated With Having An Altered BRCA2 Gene?

     

    Associated risks

    General Population risk

    With a BRCA1 gene alteration

    Breast cancer

    ~ 12% = 1 in 8 women

    60-80% lifetime risk

    Ovarian cancer

    ~1-2% = 1 in 50-100 women

    10-30% lifetime risk

    Male breast cancer

    Very low

    5-10% lifetime risk

    Prostate cancer

    ~10%

    Approximately 20% lifetime risk. Men with a BRCA2 gene alteration can develop prostate cancer earlier and it can be more aggressive

     

    There may also be a small risk of developing other cancers but not enough to warrant additional screening. However, it would be important to have a low threshold for seeking medical help for any concerning or persistent symptoms.

    *in families with a BRCA2 gene alteration and a history of pancreatic cancer, pancreatic screening is offered to family members found to have a BRCA2 gene alteration.

    What Can Be Done To Help Manage These Risks?

    For each of the high risk cancers, screening and surgical options are discussed. Different options are available to men and women, and options can also differ dependent on what age you are.

    For Women

    Breast Screening: Women who have a BRCA2 gene alteration are offered high risk breast screening. The National Institute for Health and Care Excellence (NICE) screening recommendations are for a Magnetic Resonance Imaging (MRI) scan from the age of 30 to 49 and a yearly mammogram from 40 to 69. 

    Women who opt not to be tested for the BRCA2 gene alteration, and are at 50% risk of inheriting it, are offered annual MRI scans from 30 to 49 and annual mammography from 40 to 59. These women will then join the NHS Breast Screening Programme for mammograms every 3 years from 60-70.

    Breast screening is not offered routinely to women over the age of 70 regardless of whether they carry a BRCA2 gene alteration or not (by 2016 this will be extended up to the age of 73). However screening can be requested from your local breast screening unit and is something we would recommend if you were a carrier of a BRCA2 gene alteration.   We also suggest that women carry out monthly self-examination of the breasts

    Breast Surgery: Women, who have a BRCA2 gene alteration, also have the option of having surgical removal of both breasts (bilateral mastectomy). Although this procedure could significantly reduce the risk of developing breast cancer it will not remove the risk entirely. We also recognize this is a radical step that requires careful consideration. Therefore women who choose this option are fully supported throughout the process and not rushed into making any decisions

    Ovarian Screening and Surgery: Ovarian screening involves regular blood tests approximately 3-4 times a year, to measure a marker in the blood called CA125 and also by annual ultrasound from the age of 35.

    However, ovarian screening does not reliably inform us of cancers early enough in order for them to be treated effectively.

    Therefore, for women who are BRCA2 carriers, over the age of 35/40 and have completed their families we would encourage those to think about having their ovaries and fallopian tubes removed (bilateral salpingo-oophorectomy). This can significantly decrease the risk of developing ovarian cancer but, again, the risk of cancer is never removed entirely. This may also have some impact on reducing the risk of breast cancer.  

    There are clear advantages to having your ovaries and fallopian tubes removed, however they do need to be weighed with the potential disadvantage of being put into an early menopause and the possible need for HRT. The advantages and disadvantages of HRT could be further discussed with a gynaecologist if you choose to go ahead with this process.

    Chemoprevention: Recent guidelines have suggested that ladies at high risk of breast cancer be offered chemo-prevention medications. Research suggests these medications can reduce the risk of developing breast cancer however they do have significant side effects. Please ask for a leaflet outlining the risks and benefits of chemoprevention if you think this is something you might be interested in. 

    For Men

    Men are not offered any breast screening, but we suggest they check their chest and armpit areas and seek medical advice for any unusual lumps. Prostate screening should be undertaken annually from the age of 40. We will refer you a Urology Specialist at Broadgreen Hospital who will undertake annual prostate screening for men with a BRCA2 gene alteration. Alternatively prostate screening can be provided through the GP.

    How BRCA1 Gene Alterations Are Passed Down (Inherited) Through Families?

    The way BRCA2 gene alterations are inherited is called DOMINANT inheritance. This is caused by an alteration in only one copy of the BRCA2 gene. Even though we each have 2 copies of the BRCA2 gene the normal copy cannot compensate for the altered copy and a person with one altered BRCA2 gene has an increased risk of developing cancer.

    If a parent carries an altered BRCA2 gene, each of their children has a 50%, or 1 in 2 chance of inheriting the altered gene and therefore having an increased risk of developing cancer. For each child, regardless of their sex, the risk is the same = 50%.

    What Is Predictive Testing?

    Predictive testing is offered to family members who are known to be at risk of inheriting a gene alteration that has been identified in the family but are currently well. Predictive testing is usually offered over a series of appointments to allow the opportunity to consider options and choices with time for reflection in-between. How many appointments a person requires varies considerably from person to person and is negotiated on an individual basis with your genetic counsellor team. The overall aim of the predictive testing process is to help prepare you for your results whatever they are.

    What Are The Issues To Think About When Deciding Whether Or Not To Have A Gene Test?

     

    A genetic test can establish whether you have an alteration in a gene which could affect your health.

     

    It can be difficult to make a decision about whether or not to have a genetic test. We all have gene alterations. Many of these do not affect our health. It is still quite unusual for a person to know they have an alteration in a specific gene.

    There are reasons for and against having a genetic test. Within one family, relatives often have different views. You should try to make your own decision, without feeling pressured from relatives or other influences.

    You will have plenty of opportunity to talk through the issues surrounding the test with the genetic counsellor or doctor.

    How Do You Think You Would Cope If The Test Were To Show That You Have Inherited The Altered Gene?

    For some people, knowing that they have the altered gene is preferable to living with uncertainty. Having a genetic test enables them to make decisions about the future and about screening and measures to reduce their risk. Other people may prefer not to have the test because they may feel very anxious if the test shows that they have the altered gene.

    How Do You Think You Would Cope If The Test Were To Show That You Have Not Inherited The Altered Gene? 

    Perhaps surprisingly, it can often take people some time to get used to the knowledge that they do not have the altered gene. This can be particularly difficult when other relatives have a different result.

    People who do not have the altered gene have the same chance of developing cancer as other people in the general population.

    If The Test Were To Show That You Have The Altered Gene, This Would Mean That Your Children Would Also Be At Risk Of Having The Altered Gene. How Do You Think You Might Feel About This? 

    Having a genetic test may be important to other people, such as your children. It will help them to understand their own risk and if necessary make choices about screening and risk reducing options.

    It can be very difficult knowing that you could have passed on an altered gene to your children. This can be hard to deal with even if you know that you had no control over which genes you passed on

    If You Were To Have The Test, Would You Want To Tell Anyone The Test Results? 

    It is important to think about who you would want to know about your test as it is very personal information. Many people who attend our clinic find that it helps to confide in a partner, trusted friend or relative.

    Would Having The Test Affect Your Ability To Get Life Or Medical Insurance?

    At present, if you have already obtained your insurance, having the test should not affect your current policies. However, it is not possible to know whether it will affect your ability to get or to change insurance policies in the future.

    Would Having The Test Affect Your Employment?

    If the test shows you have the altered gene it would be your decision whether or not to inform your present employers. Some employers might ask about this if you apply for a new job.

    It is important that each family member makes the decision that is best for them. We will support you whether you decide to have the test or whether you decide against having the test. It is your decision!

    What Happens If I Choose To Go Ahead And Have A Test?

    - After you have the opportunity to discuss the positives and negatives of predictive testing, if you wish to have the test you will be asked to read and sign a consent form and a small blood sample will then be taken.

    - Once the blood is taken, the laboratory staff would test the sample to find out whether or not you have inherited the altered gene known in your family.

    -Test results are usually available 4-6 weeks after having your blood taken and you can choose to have your results over the phone or in a clinic appointment.

    If, for some reason you, have not received your results within 4-6 weeks as expected please call the clinical genetics department on 0151 802 5008. Please remember to have your g number and w number handy for this call so we can quickly and correctly identify you.

    What Happens If I Choose Not To Go Ahead With Having A Test? 

    --We may still recommend screening to you as explained earlier in this leaflet.

    You can change your mind and decide not to have the test at any time before the result is given.

    Other Factors to Consider

    Insurance and Genetics

    For some types of insurance it is necessary to provide medical information, including genetic information, to the insurers in order for them to set up your policy and work out your premiums. The types of policy that require a medical history or genetic test are likely to be, life cover, critical illness insurance and income protection insurance.

    We would suggest that if yourself or family members are considering taking out new insurance policies in the future that consideration be given to the possible affect genetic test results could have on the ability to gain insurance or the premiums charged. Genetic Test results do not affect insurance policies already in place.

    The Association of British Insurers (ABI) has a Code of Practice ‘The Concordat and Moratorium on Genetic and Insurance’.

    • Insurance companies cannot ask for the Predictive Genetic Test results of individuals or family members (unless for Huntington Disease over £500,000). A Predictive Genetic Test is where an individual has a family member with a genetic condition, but who personally has no symptoms, signs or abnormal medical tests consistent with the condition at time of testing.
    • If a family member has been diagnosed with a genetic condition based on a Diagnostic Genetic Test then you or family members will need to mention this when asked to provide your family’s medical history. In many cases Diagnostic Genetic Testing is used to confirm a diagnosis when a particular condition is suspected because of symptoms, signs or abnormal non-genetic tests including unusual findings on a routine blood test or other test.

     

    Sources of Further Information Include

    The Association of British Insurers Genetics Frequently Asked Question’s https://www.abi.org.uk/products-and-issues/topics-and-issues/genetics/genetics-faqs/

    Genetic Alliance UK (Charity) Genetics & Insurance http://www.geneticalliance.org.uk/information/living-with-a-genetic-condition/insurance-and-genetic-conditions/

    Family planning-

    Everyone who has an inherited genetic condition can choose from a variety of options to ensure they do not pass it on. It is a highly personal decision and there is certainly no expectation that couples have to do anything to prevent passing on a BRCA1 gene alteration, but for couples who wish to consider this, some of the choices can include:

    • Preimplantation genetic diagnosis (PGD)

    PGD involves the use of assisted reproductive technology (ART)|, which is also offered to couples with fertility problems. The aim is to obtain and fertilize a number of eggs. Once fertilized, the embryos develop for six days and then a number of cells are removed from each embryo. The genetic material (DNA or chromosomes) within each cell is then tested for the genetic or chromosome abnormality. Up to two unaffected embryos are then transferred to the uterus with the hope that they will implant and form a pregnancy. If successful, the baby should not be affected by the disorder it was tested for.

    More information can be obtained http://www.pgd.org.uk

    • Adoption
    • Sperm or egg donation: dependent on who carries the gene alteration.

    Our experience is however that very few couples who carry a BRCA1 gene alteration choose any of the above options.

    Oral Contraceptives

    There have been a number of studies looking at the relationship between taking oral contraceptives and breast cancer risk but unfortunately the findings can often differ between different studies. However, overall, we know that taking the combined oral contraceptive pill (COC) increases the risk of breast cancer in all women. The risk appears to be confined to current and recent use and the risk drops once you stop taking the pill, and will return to normal after a number of years without use. It is felt that 10 years after stopping the COC, the breast cancer risk is the same as if you had never taken it at all.

    Use of COC also reduces the risk of ovarian cancer proportionally to the duration of use but should never be prescribed for this reason only.

    There is no evidence regarding progesterone only contraceptives and breast cancer risk associated with family history.

    You should discuss the use of oral contraceptives with your GP to weigh up the risks and benefits to help you make the decision that is right for you. You may also want to look at the Cancer research UK website for further information

    Useful websites

    Genetic Alliance UK                                                                www.geneticalliance.org.uk

    Cancer research group UK (CRUK)                                      www.cruk.org.uk

    National Institute for Health Care and Excellence (NICE)      www.nice.org.uk/Guidance/CG41

     

    All images in this leaflet were provided by NHS National Genetics and Genomics Education Centre

  • Information for Men from Families with a Known Alteration in the BRCA2 Gene

    The leaflet is detailed below, or you can download the 'Information for men from families with a known alteration in the BRCA2 gene' leaflet in PDF.

    Breast Cancer

    In the UK, breast cancer affects 1 in 8 women during their lifetime (Cancer research UK July 2012). Most of these women are aged over 60. It is very rare for men to develop breast cancer.

    Ovarian Cancer

    Ovarian cancer is less common. In the UK, about 1 in 50 women are affected during their lifetime (Cancer research UK July 2012). Most of these women have been through the menopause.

    Prostate Cancer

    It has been estimated that the lifetime risk of prostate cancer is around 1 in 8 for the men in the UK (Cancer research UK July 2012). It is strongly related to age and very few men under the age of 50 will be diagnosed with prostate cancer. Around three quarters of cases occur in men over 65 years with the largest number diagnosed in those aged 70-74.

    What is Inherited Cancer?

    In some families, women over several generations develop breast or ovarian cancer. Sometimes in these families men may also have had a prostate cancer. As this cancer is fairly common, especially in men over the age of 75, it may not be linked to breast or ovarian cancers. Occasionally men in these families have had breast cancer.

    In a very small number of families some relatives may have inherited a gene alteration making them more likely to get cancer.

    What are Genes?

    Our genes are the unique set of instructions inside our bodies which makes each of us individual. There are many thousands of different genes, each carrying a different instruction. As well as determining how we look, our genes control the way each cell or building block of the body works. Specific genes control specific cell types. Some genes are particularly important in controlling the way the cells in the breasts and ovaries grow. These genes may also be important in the growth of cells in the prostate.

    We inherit two copies of each of our genes, one from our mother and one from our father.

    Why do Some Genes Increase the Risk of Cancer?

    The instructions in each gene are like a code. Sometimes the code differs from that of a normal gene

    For example imagine the normal code for a gene is:

    1-2-3-4-5-6-7-8-9-10-11-12-13-14

    The gene passed down through the family may have a slightly different code:

    1-2-3-4-5-6-7-8-9-9-10-11-12-13-14 

    This gene will give slightly different instructions to the cells it controls than a gene with a normal code. We call this an altered gene.

    If the altered gene is one that controls breast, ovarian and possibly prostate cells, there is a higher chance that breast, ovarian or prostate cancer may develop. 

    How can an Altered Gene be Inherited?

    If one parent (either the mother or the father) has an altered BRCA2 gene, this can be passed down to a child.

    Each child has a 50/50 chance of inheriting that parent's altered gene and a 50/50 chance of inheriting that parent's normal gene.

    Which Gene Increases the Risk of these Cancers?

    The two genes which we know are important in breast, ovarian and possibly prostate cancer when they are altered in this way are called BRCA1 and BRCA2. There may be other important genes which have not yet been discovered.

    What if a Man Inherits an Altered BRCA2 Gene?

    If a man inherits an altered BRCA2 gene his lifetime risk of developing prostate cancer is increased up to 20%. He also has a slightly increased risk of developing breast and possibly other cancers.

    What Screening is Available for men who Carry the Altered Gene, or who are at 50/50 Risk of Having the Altered Gene?

    Although no breast screening is available to men with a BRCA2 gene alteration, we do advise that men check their breast and armpit area for any lumps and report any concerns to their GP.

    No screening test for prostate cancer has been shown to detect all cases of cancer and sometimes results of tests can be abnormal, even in men who do not have cancer. This can cause a great deal of anxiety as well as unnecessary investigations. However, if a man is found to be at increased risk of prostate cancer he can discuss screening with his GP who will advise him about what is available locally. 

    Prostate screening involves examination of the prostate and a blood test. To examine the prostate, the doctor inserts a finger into the back passage to check that the prostate is not enlarged. The blood test measures the level of a substance called PSA (Prostate Specific Antigen) that is raised in prostate cancer.

    Cheshire and Merseyside Clinical Genetics Service

    Liverpool Women’s Hospital

    Crown Street

    Liverpool, L8 7SS

    Telephone 0151 802 5001 or 5002

    Facsimile: 0151 702 4283

  • Chromosome Inversions

    The leaflet is detailed below, or you can download the 'Chromosome Inversions' leaflet in PDF.

    Introduction

    This leaflet is written for individuals who have a chromosome inversion and for members of their family. It is intended to explain what a chromosome inversion is, what it means for the individual, for their wider family.

    What are Genes and Chromosomes?

    Genes are tiny 'packages' of vital information which influence our growth and development. Each person has approximately 20,000 pairs of genes, which work rather like special computer programmes, and determine features such as the colour of our eyes, how many fingers and toes we have, how tall and short we are, and so on. Genes are so small that they cannot be seen, even under a powerful microscope. They are arranged along little threadlike strands, rather like the way that beads are arranged along a string. These strands are called chromosomes, and are inside most of the cells in our body. Unlike genes, chromosomes can be seen under a microscope.

    A person usually has 46 chromosomes in each cell, arranged in 23 pairs. We inherit one of each pair of chromosomes from our mother and the other from our father. This is how we inherit characteristics from our parents.

    To help differentiate between chromosomes, each pair has been given a number. The number 1 chromosomes are the largest, the number two are the next largest and so on right down to the number 22 which are the smallest. The remaining pair (X and Y) are called the sex chromosomes and determine person is male (XY) or female (XX).

    What are Chromosome Inversions?

    Occasionally a chromosome will break in two places and the piece which is broken rejoins UP SIDE DOWN. Therefore, a person with a chromosome inversion will have one ‘normal’ chromosome and a chromosome with an inversion where the genes are in a different order compared to the other chromosome. People who have a chromosome inversion have no extra or missing genes and are expected to develop normally as it does not really matter which order the genes are in as long as they are all present. If a person has a chromosome inversion it can, however, cause problems when the individual comes to have children. Each person passes on half of their chromosomes to their children. At conception an egg (with 23 chromosomes) joins with a sperm (also with 23 chromosomes) to make an embryo.

    Usually, before each chromosome pair splits up to make and egg or sperm they line up closely together and sometimes exchange genes in a process called a crossover. To enable each of the genes to pair up with its partner on the opposite chromosome, one chromosome needs to form a loop. If there is a crossover between the chromosomes within the loop, an imbalance in the number of genes will occur. Therefore, when chromosomes pair up before separating into an egg or sperm one of three things might happen:

    1 - The parent with an inversion passes their ‘normal’ chromosome into the egg or sperm, so the baby will have the correct number of genes in the correct order.

    2 - The parent with the inversion passes their chromosome with the piece which is inverted into the egg or sperm. The baby will inherit the inverted chromosome; however, as the correct amount of genetic material will be present the baby will not have any learning or developmental issues due to their parents chromosome inversion.

    3 - If a loop and crossover has occurred whilst the egg or sperm were being formed, a baby could inherit a chromosome which is carrying an incorrect number of genes. This may result in an early miscarriage or problems with infertility. A child who has inherited either too much or too little genetic material will usually have physical and/or learning difficulties.

    If we know a parent carries a chromosome inversion there are tests are available in pregnancy that enable us to check the chromosome pattern of the developing baby to determine if it is carrying the correct amount of genetic information. These tests are called amniocentesis and chronic villus sampling (CVS) and there are separate leaflets available which explains these tests in more detail.

    Some couples may be eligible for preimplantation genetic diagnosis (PGD). PGD involves checking the chromosomes of embryos created through IVF. Only embryos with the correct amount of genetic material are transferred into the womb with the hope it develops into a baby.

    How can Someone Find out if They Carry a Chromosome Inversion?

    If you are aware someone in your family carriers a chromosome inversion you can request a referral into your local genetic service via your GP. Your genetic counsellor will arrange a blood test to look at your chromosome pattern

    If you need more advice about any aspect of chromosome inversions, you are welcome to contact:

    Cheshire and Merseyside Clinical Genetics Service

    Liverpool Women’s Hospital

    Crown Street

    L8 7SS

    Telephone 0151 802 5001 or 5002

    Facsimile: 0151 702 4286

  • Chromosome Translocations

    The leaflet is detailed below, or you can download the 'Chromosome Translocations' leaflet in PDF.

    Introduction

    This leaflet is written for individuals who have a chromosome inversion and for members of their family. It is intended to explain what a chromosome inversion is, what it means for the individual, for their wider family.

    What are Genes and Chromosomes?

    Genes are tiny 'packages' of vital information which influence our growth and development. Each person has approximately 20,000 pairs of genes, which work rather like special computer programmes, and determine features such as the colour of our eyes, how many fingers and toes we have, how tall and short we are, and so on. Genes are so small that they cannot be seen, even under a powerful microscope. They are arranged along little threadlike strands, rather like the way that beads are arranged along a string. These strands are called chromosomes, and are inside most of the cells in our body. Unlike genes, chromosomes can be seen under a microscope.

    A person usually has 46 chromosomes in each cell, arranged in 23 pairs. We inherit one of each pair of chromosomes from our mother and the other from our father. This is how we inherit characteristics from our parents.

    To help differentiate between chromosomes, each pair has been given a number. The number 1 chromosomes are the largest, the number two are the next largest and so on right down to the number 22 which are the smallest. The remaining pair (X and Y) are called the sex chromosomes and determine person is male (XY) or female (XX).

    What are Chromosome Translocations?

    Sometimes when cells are dividing during egg or sperm formation, or in the very early development of the baby, one or more chromosomes can break and if they do not re­join in the correct position this causes an unusual arrangement of the chromosomes known as a translocation. There are two different types of translocation:

    1. Reciprocal translocation A Reciprocal translocation occurs when two fragments break off from two different chromosomes and swap places, as shown in this diagram.
    2. Robertsonian translocation A Robertsonian translocation occurs when two whole chromosomes become stuck together, as shown in this diagram.

    To understand why translocations can be important in health and development, it is helpful to understand the difference between BALANCED and UNBALANCED translocations.

    Balanced Chromosome Translocation

    If the chromosome material has been rearranged in such a way that no chromosome material has been lost or gained it is known as a balanced translocation. The health of a person who carries a balanced rearrangement of their chromosomes is NOT affected by it. However, it may become important when they come to have children as there is a possibility a baby can inherit an unbalanced translocation.

    Unbalanced Chromosome Translocation

    If one parent carries a balanced translocation, when they make their eggs or sperm it is possible for their child to inherit a rearrangement of their genetic material resulting in an extra piece of one chromosome and/or a missing piece of another chromosome. A child who has inherited either too much or too little genetic material will usually have physical and/or learning difficulties.

    If A Parent Has A Balanced Translocation Will He/ She Always Pass It On?

    Not necessarily as there are several possible outcomes for the pregnancy:

    1. The parent with the translocation passes their ‘normal’ chromosomes into the egg or sperm, so the baby will have the correct number of genes in the usual order.
    2. A baby may inherit the same balanced translocation as the parent. In this case the child would be expected to be a healthy as they have all their genetic information present.
    3. A baby may inherit an unbalanced form of the translocation. A child who has inherited too much or too little genetic material will usually have physical and/or learning difficulties.
    4. The pregnancy may end in a miscarriage.If we know a parent carries a chromosome translocation there are tests available in pregnancy that enable us to check the chromosome pattern of the developing baby to determine if it is carrying the correct amount of genetic information. These tests are called amniocentesis and chronic villus sampling (CVS) and there are separate leaflets available which explains these tests in more detail.How Can Someone Find Out If They Carry A Translocation?
    5. If you are aware someone in your family carriers a chromosome translocation you can request a referral into your local genetic service via your GP. Your genetic counsellor will arrange a blood test to look at your chromosome pattern.
    6. Some couples may be eligible for preimplantation genetic diagnosis (PGD). PGD involves checking the chromosomes of embryos created through IVF. Only embryos with the correct amount of genetic material are transferred into the womb with the hope it develops into a baby.
    7. Therefore, it is possible for a person who carries a balanced translocation to have healthy children, however, their risk of having a child with a learning or physical disability is higher than average. The precise risk depends on where in the chromosomes the translocation has occurred.

    If you need more advice about any aspect of chromosome inversions, you are welcome to contact:

    Cheshire and Merseyside Clinical Genetics Service

    Liverpool Women’s Hospital

    Crown Street

    L8 7SS

    Telephone 0151 802 5001 or 5002

    Facsimile: 0151 702 4286

  • Welcome to Clinical Genetics

    The leaflet is detailed below, or you can download the 'Welcome to Clinical Genetics' leaflet in PDF.

    Genetics

    The Merseyside and Cheshire Clinical Genetics Service is primarily involved with the diagnosis and genetic counselling of families with possible or known inherited disorders. The service is managed and delivered by Liverpool Women’s NHS Foundation Trust.

    Staffs are available to answer any additional questions you might have ahead of your appointment. We can be contacted on:

    0151 802 5001 / 5002

    When you visit us, you may meet:

    • A Clinical Geneticist, or trainee Geneticist; a doctor who has experience of a wide range of genetic conditions.
    • A Registered Genetic Counsellor, or trainee Genetic Counsellor; a professional with specialist training in genetics and counselling skills.
    • Our administration and clerical team.

    What We Do

    From your initial appointment, we will provide as much information as possible about your reason for visiting us and discuss the options and course of actions that are right for you and your family. Not everyone who comes to our service has a genetic condition.

    We help individuals and families by:

    • Making, confirming or excluding a diagnosis.
    • Providing understandable information about a condition.
    • Discussing the impact of a condition in the future.
    • Discussing the risks to future children and/or other family members
    • Explaining types of testing or screening available.
    • If appropriate we can also talk about ways of living with a condition and the medical and social support available.

    Reasons for Referrals

    There are a variety of reasons why people are referred to us. Here are some of them:

    • A known condition runs in your family and you may be concerned about your chances of developing the condition. Equally you may be concerned about passing it on to your child and future generations.
    • You or your partner have a child with a combination of problems where diagnosis may be uncertain and either you or your doctors are wondering if there may be a genetic cause for this.
    • You, your partner or your family has experienced pregnancy loss.
    • You and your partner are close blood relatives.
    • You have a family history of particular types of cancer.

    Making an Appointment – Step-By-Step Guide

    • As well as this leaflet, you will have received a referral letter asking you to contact the Clinical Genetics Department to opt into our service and to make an appointment. Please note: If you do not contact us after receiving the enclosed letter you will not receive an appointment.
    • When you phone the Clinical Genetics Department one of our clinic coordinators will arrange your first appointment.
    • Depending on the reason for your referral, you will be offered an appointment either in a telephone clinic, or a hospital clinic. Genetic clinic appointments are held at various hospital sites across Cheshire and Merseyside. Please study the appointment letter carefully, for details of your appointment location and time.

    What to Expect Next

    Prior to your appointment, you may be contacted by a member of our Family History Collection Team. This helps in gathering information about your family history and getting confirmation of family members’ diagnoses, so that risk assessments and information you are given at your appointment, are as accurate as possible. 

    Your appointment will be with a Genetic Counsellor, Trainee Genetic Counsellor, Consultant Geneticist or Trainee Geneticist.

    Genetic counselling is integral to the genetics contact and is part of any new referral. It is a communication process that responds to your questions and concerns, and helps with the interpretation and understanding of information provided during your appointments. 

    At your appointment, the clinician that you meet will either review your family history if we already know it, or will take your family history. We may need details from both sides of the family including grandparents, aunts, uncles and cousins. This is necessary to enable us to provide you with accurate information. It is also an opportunity for you to share any concerns you might have or to ask any questions. Your partner, relative or friend is welcome to accompany you at your appointments. If you have hearing difficulties or your first language is not English, we can arrange for an interpreter to be present.

    Some patients require more than one appointment, especially those who are considering having a predictive genetic test, for a hereditary condition known to be in their family. The clinician will discuss this at the first appointment. 

    On occasion, student clinicians may be present for training purposes. If you rather they weren’t, please notify a member of staff. 

    If for any reason you cannot attend your appointment, please contact the department referenced on the appointment letter. We can then arrange another date for you and offer your original appointment to someone else. 

    Please note: Anyone failing to attend an appointment or who cancels more than once will be discharged back to their referring clinician. This does not affect your right to request a future referral to our service.  

    If you need more advice about any aspect of your referral into Clinical Genetics, you are welcome to contact:

    Cheshire and Merseyside Clinical Genetics Service

    Liverpool Women’s Hospital NHS Foundation Trust 

    Crown St. Liverpool, Merseyside L8 7SS 

    Telephone 0151 802 5001 or 5008

    Facsimile: 0151 702 4283

  • Dominant Inheritance

    The leaflet is detailed below, or you can download the 'Dominant Inheritance' in PDF.

    What Are Genes? 

    Genes are the unique set of instructions inside our bodies which make each of us an individual. There are many thousands of different genes, each carrying a different instruction. If a gene is altered, it can cause a genetic condition or disease. This gene alteration is sometimes known as a mutation. 

    We have two copies of each gene. One copy is inherited from each of our parents. When we have children, we pass on only one copy of each of our genes. 

    What Does Dominant Inheritance Mean? 

    Some genetic conditions are passed on in the family in a dominant way. These conditions are caused by an alteration in one copy of a gene. They are called dominant because the altered copy of the gene is dominant over the other copy of the gene. 

    Having Children 

    If a parent carries an altered gene for a dominant condition, each of their children has a 50%, or 1 in 2 chances of inheriting the altered gene and being affected by the condition. For each child, regardless of their sex, the risk is the same = 50%. 

    In some dominant conditions, it is possible to inherit an altered gene without showing any symptoms of the condition. Even within a family, some individuals may be affected by the same dominant condition in different ways. 

    Some dominant conditions are known as "late onset disorders". In other words, they only affect individuals in adulthood. 

    In some families, an isolated case of a dominant disorder may be the result of a new mutation (a change which arises for the first time) in either the egg or the sperm that went to make that child.

    If you need more advice about any aspect of Dominant Inheritance, you are welcome to contact:

    Cheshire and Merseyside Clinical Genetics Service Liverpool Women’s Hospital

    Crown Street

    Liverpool, L8 7SS

    Telephone 0151 802 5001 or 5002

    Facsimile: 0151 702 4286

  • Familial Adenomatous Polyposis (FAP) in the family

    The leaflet is detailed below, or you can download the 'Familial Adenomatous Polyposis (FAP) in the family' in PDF.

    What is Familial Adenomatous Polyposis (FAP)?

    FAP is a condition which runs in families, hence the term "familial". The rest of the name comes from the fact that little lumps called polyps, grow in large numbers on the lining of the bowel. The polyps themselves are not cancerous, but people who have FAP will eventually develop cancer if they do not receive treatment.

    What Is A Polyp?

    Polyps are non-cancerous lumps, or tumours, which grow on the surface of the bowel. There are many different kinds of polyp which grow in a number of places in the body, but the polyps we see in the bowel of people with FAP are called adenomas. Bowel polyps are found in many people without FAP, but usually just a few polyps are found. A diagnosis of FAP is made when large numbers of adenomas are found in the large bowel, which is the end of the long food pipe of the body which we call the colon and rectum. The following diagram shows where the colon and rectum are in the body, and what the polyps look like inside the bowel.

    How is FAP inherited?

    FAP is due to a fault in a gene that can be passed down families form a parent to their child. Genes are messages which control the working of the body and decide things like the colour of our eyes. Think of genes as recipes. The recipes allow the body to make chemical tools and building blocks. If part of the recipe is missing or has been copied incorrectly, that part of the body will not be able to do its job properly.

    Most genes come in matching pairs, with a copy of each gene coming from the mother’s egg and a copy from the father's sperm. We think that everyone has at least one gene which doesn't work, but usually the spare copy from the other parent is enough to get by on. Some genes seem to be so important that you need both copies working to remain healthy. One faulty copy of a gene of this type can cause disease, so we call this gene dominant because it shows itself despite the presence of a normal copy. 

    FAP is one of the more frequent dominant genetic problems, but it is still uncommon, affecting about one person in every 8,000.

    If someone has FAP it means that they have a working copy and a faulty copy of the gene. Each time they have a child there is a 50:50 chance that they will pass on the working copy and a fifty-fifty chance that they will pass on the faulty copy.

    How Do We Know Who Has FAP?

    Most people who have the gene for FAP begin to develop polyps in the colon in their early teens, so bowel checks should start between 10 and 14 years of age. Most people with FAP have developed polyps by the age of 30, and with every passing year without polyps, the likelihood that they have inherited the working copy of the gene increases.

    The FAP gene has other effects on the body as well as causing polyps to appear. Some people get skin cysts, and some get harmless bumps on their bones.

    For some reason, which we don't understand, most people get small black dots at the back of the eye which we call CHRPEs (this stands for congenital hypertrophy of the retinal pigment epithelium, but no-one ever calls them that!). These do not affect vision in any way. A lot of people who do not have FAP have one or two of these black dots, but if there are more than five, or a large distinctive area, then this is a good indication that the person carries the FAP gene. If CHRPEs do not run in your family with polyps, then a clear eye examination does not mean that you do not carry the gene. There are different ways we can decide who has FAP; look for polyps, look for CHRPEs, do gene tests, or look for bony lumps or cysts.

    The only way we can be sure that anyone has FAP is if we find a lot of polyps, or if we can prove that a person carries a faulty copy of the gene.

    Gene Tests

    If we think of a gene as a long word carrying a message, then the FAP gene has nearly 9000 letters in it. In different families it is a different letter or group of letters which have been wrongly copied which causes the gene not to work. The genetics team will try to work this out for each family, and if we find the "spelling" mistake we will offer a test to the rest of the family to find out who has it and who has not.

    Blood cells contain copies of all your genes, so we can test the FAP gene from a blood sample. If a blood sample is not possible, saliva or other samples can sometimes be used.

    Those who do not have the faulty copy of the gene can stop bowel screening, and they cannot pass FAP to their children. Those who do have the faulty copy will continue with regular screening as before, until polyps are found.

    For some families we cannot offer a gene test. This may be because we have not yet found the fault in the gene in that family, or it may be that no one is available who has FAP to test. If no gene test can be done, you will be advised to carry on with regular bowel checks.   

    Looking For Polyps

    A short tube can be passed through the back passage into the lower part of the bowel. This examination is called a sigmoidoscopy, and you will be able to go home from hospital on the same day.

    A longer, flexible tube can be used to examine more of the bowel, and this procedure is called a colonoscopy. 

    Doctors may use either method, but for colonoscopy, it is necessary to prepare the bowel by emptying it before the test. The hospital will give you details about this, but it usually involves taking a liquid medicine the day before the check, and sticking to a low bulk diet for a few days to ensure that the bowel is quite empty.

    What Happens If Polyps Are Found?

    Usually the doctor will take a sample of the lining of the bowel, or from a polyp, to be examined under the microscope. If these are harmless, it is sometimes reasonable to carry on with regular checks. However, most doctors offer the choice of having an operation if they find a large number of polyps. Many people choose to have an operation as soon as polyps are found, rather than wait until there are large polyps.

    The Three Main Operations To Remove The Colon Are:

    An Ilea-rectal anastomosis (IRA) involves removing the large bowel and attaching the small bowel to the rectum. This allows you to go to the toilet normally, but sometimes this can be many times a day. The rectum, which remains intact, may develop polyps so this must be examined at least once a year to prevent a cancer starting there.

    A pouch operation involves the removal of the lining of the rectum when the colon is removed. A pouch is then made from the end of the small bowel, which then takes over some of the work of the colon. No checks have to be made on the rectum as there is no lining to grow polyps.

    A pan-procto colectomy is done when the rectum has to be removed. The end of the small bowel is brought to the surface and the waste material is collected in a disposable bag.

    Where Else Could Problems Occur?

    People with FAP also develop polyps in the small intestine. Screening by endoscope from 25 will detect polyps and guide further management. Between 4 and 12% of patients develop cancer of the small intestine.

    Is There A Cure?

    Research is ongoing to try to develop new treatments.

    Doctors are also looking at non-surgical ways to stop polyps growing, such as drug treatment, and these may be recommended in certain circumstances.

    These options may offer an opportunity to treat polyposis without surgery in the future but the only safe option at the moment is an operation.  

    Explanation of Unfamiliar Words:

    FAMILIAL Something which runs in families.

    POLYP A non-cancerous lump on the bowel wall.

    ADENOMA (Adenomatous) there are different kinds of polyp: this describes how the polyps in FAP look under the microscope.

    LARGE BOWEL The end section of the intestine or food pipe made up of colon and rectum.

    GENE One of the chemical recipes which control the working of the body. 

    DOMINANT Only one of a pair of genes is faulty.

    CHRPE (Congenital hypertrophy of retinal pigment epithelium). Harmless black marks on the back of the eye.

    SIGMOIDOSCOPY A short tube with a light at the end is passed into the rectum and the last part of the colon to look for polyps.

    COLONOSCOPY Like sigmoidoscopy, but the whole colon is seen.

    APC The name scientists give the FAP gene. It stands for adenomatous polyposis coli.

    COLECTOMY An operation to remove the colon, leaving the rectum in place.

    ILEO-RECTAL ANASTAMOSIS (IRA) The small bowel is attached to the rectum when the colon has been removed.

    POUCH A similar operation to IRA but the lining of the rectum is also removed and is replaced by lining from the small bowel.

    PAN-PROCTO COLECTOMY (PPC) The colon and rectum are removed and the small bowel is brought to the surface of the abdomen.

    ILEOSTOMY When someone has a PPC operation, the waste material is collected in a disposable bag.

    DESMOID A non-cancerous tumour which may grow in the abdomen leading to pain and obstruction. 

    Who Should I Contact For Further Advice? 

    The first person you should ask if you have any health problems is your family doctor. It may be that he/she is not very familiar with this problem, so you should take along this fact sheet. If anyone in your family has FAP, then they will have a surgeon, and you could ask them for advice. Every region in the UK has a genetics service and they can be contacted for help via your GP or directly for advice.

    If You Need More Advice About Any Aspect Of FAP, You Are Welcome To Contact:

    Cheshire and Merseyside Clinical Genetics Service

    Liverpool Women’s Hospital NHS Foundation Trust

    Crown Street

    Liverpool

    L8 7SS

    Telephone 0151 802 5003 or 5008

    Facsimile: 0151 702 4286

  • Insurance and Genetics

    The leaflet is detailed below, or you can download the 'Insurance and Genetics' in PDF.

    Introduction

    For some types of insurance it is necessary to provide medical information, including genetic information, to the insurers in order for them to set up your policy and work out your premiums. This leaflet outlines answers to questions you may be asking about how genetic tests could affect your insurance.

    Do I Have To Tell The Insurance Company About A Hereditary (Genetic) Disease That Runs In My Family?

    If it is requested on your insurance application form, then you must give the insurers any information about current or previous illness amongst family members. However, you only need to answer the questions that are on the form.

    Will The Insurance Company Ask Me To Have A Predictive Genetic Test?

    No. The Association of British Insurers (ABI) has a Code of Practice on Genetic Testing that states that people seeking insurance must not be asked to have a genetic test in order to get insurance.

    If One Of My Relatives Has A Genetic Test, Do I Have To Tell The Insurance Company?

    No. Relative’s predictive genetic test results cannot be counted in the decision to offer you insurance. However, you do need to include all details about any illnesses that run in your family if the application form requests that information.

    I Have Already Had A Predictive Genetic Test? Do I Have To Tell My Insurance Company The Results Of This Test?

    British Insurers have agreed to a moratorium lasting until 2017, which states that you can apply for a total of up to £500,000 of life insurance and up to £300,000 of certain types of health insurance (critical illness, income protection or long-term care insurance) without having to tell your insurers the result of previous genetic tests. Above these amounts you need to tell the insurer the result of a predictive genetic test when answering the insurer's questions. These questions only apply to genetic tests that are approved by the Government's Genetics and Insurance Committee (GAIC) as being relevant to the type of insurance you want. An up-to-date list of approved genetic tests can be obtained from the Genetics and Insurance Committee website: www.doh.gov.uk/genetics/gaic/index.htm.

    Do I Have To Tell My Insurers About Any Predictive Genetic Tests That I Have In The Future?

    No - not for existing policies. But it is important to tell insurers all of the relevant information that is asked for when you apply for new insurance. If you need to claim later on, insurers can withhold payment if they believe you deliberately failed to inform them of relevant medical information in your original application.  

    What Happens If I Have A Predictive Genetic Test And The Result Is Negative, Which Means I Have Not Inherited A Genetic Disease That Runs In My Family?

    You may tell an insurance company about a negative test result if you wish. Many insurance companies take this into account when working out your policy. This may vary with different companies.

    What Will Insurance Companies Do With My Predictive Genetics Result?

    Your genetic information is private, and insurers are required to adhere to data protection legislation and ABI rules. Any genetic information about you is securely locked away and only brought out by the staff that needs to use it in order to prepare your policy. Any genetic information that you provide is confidential, and will not be shared with any other insurance company unless you agree to it. The genetic information is destroyed when it is no longer relevant, so you don't need to worry about it being passed onto other agencies.

    Can Insurance Companies Really Interpret My Genetic Test Results Properly?

    Insurance companies employ staff and medical experts who are trained in the interpretation of medical information and test results. If you believe that your results have been interpreted incorrectly, you should contact the insurance company to ask for a reassessment.

    I Have Been Asked To Take Part In A Genetics Research Project. Could This Affect My Current Or Future Insurance?

    No. The Association of British Insurers has officially stated that their members would not be interested in any test results produced by research projects. First, no research will affect any policy you have already taken out. Second, only tests where you know the results could, even in principle, affect any future insurance. With many research projects participants are not told their test results, because these are not relevant to any health concern. Third, even if you do know the results, the ABI has confirmed that insurers will only consider results of tests done as part of a clinical diagnostic process and approved by the Government's Genetics and Insurance Committee.

    It is most unlikely that the committee would approve using research tests. You should not let worries about insurance put you off from helping with research if you wish to.          

    If You Require Any More Advice about Any Aspect of Genetics and Insurance You Are Welcome to Contact;

    Cheshire and Merseyside Clinical Genetics Service

    Liverpool Women’s Hospital NHS Foundation Trust

    Crown Street

    Liverpool

    L8 7SS

    Tel; 0151 802 5001/5002

    Fax; 0151 802 5096    

    ABI Website - Https://Www.Abi.Org.Uk/Products-And-Issues/Topics-And-Issues/Genetics/Genetic-Testing/

    ABI helpline - 020 7216 7455

    Genetic Alliance- Http://Www.Geneticalliance.Org.Uk/Information/Living-With-A-Genetic-Condition/Insurance-And-Genetic-Conditions/

    Telephone: 020 7704 3141

  • Klinefelter Syndrome (XXY)

    The leaflet is detailed below, or you can download the 'Klinefelter Syndrome (XXY)' in PDF.

    Introduction

    Humans are usually born with 46 chromosomes, which are arranged in 23 pairs. One of these pairs determines whether a baby is male or female, and these are known as the sex chromosomes. Boys are boys because they are born with the sex chromosomes XY, and girls are girls because they are born with two X chromosomes (XX).

    Occasionally, a boy is born with an extra X chromosome. This is known as Klinefelter Syndrome. The picture above is an enlarged photograph of chromosomes from someone with Klinefelter Syndrome.

    About 1 in 600 boys have an extra X chromosome, but often they are unaware of it. Even though these boys have an extra X sex chromosome, they are genetically male and will often not realize they have this extra chromosome, but occasionally it can cause problems that may require treatment.

    What causes Klinefelter syndrome?

    The condition is named after an American doctor called Dr. Harry Klinefelter who first described the condition in 1942.

    The vast majority of parents with a son with Klinefelter Syndrome have normal chromosomes themselves. The extra X chromosome is present due to a "genetic mistake" occurring at the time of cell division to produce the egg or sperm that went to make that baby. In other words, the condition occurs by chance and the causes are not known. There is a slightly higher risk of the condition occurring in the children of older mothers. This, however, only accounts for a minority of cases of boys with Klinefelter Syndrome. 

    Will it Happen Again? 

    This is very unlikely.

    Some parents do, however, opt to have a test in a future pregnancy to check the chromosomes of the baby. The need for testing and how this is carried out can be discussed at a genetics clinic. 

    How does it affect the child?

    Possible features may include: 

    Babies 

    Baby boys with Klinefelter Syndrome look completely normal at birth. Research has shown that they may be slightly smaller than babies with normal chromosomes. The genitals appear normal, although often one or both testicles will not have come down into the scrotum (an undescended testicle). This may need to be corrected by a minor operation in the first few years of life. 

    Toddlers 

    Children with Klinefelter Syndrome usually sit, crawl and walk at the usual time, but they may be slower to learn to talk than other children. If this is a problem, then speech therapy will be helpful and can start when the child is between 3 and 4 years old. 

    School children 

    Research has shown that the average intelligence (sometimes known as IQ) of boys with Klinefelter Syndrome is lower than that of boys with the usual number of chromosomes. In one study, the average IQ score was 98 for boys with Klinefelter compared with a value of 112 in the other boys. However, the range of IQ values in boys with Klinefelter Syndrome was 70 to 130, so it is clearly possible to have above average intelligence with this condition. 

    Boys with Klinefelter Syndrome tend to do less well at school than their brothers and sisters, and may feel discouraged by this. It is important to try not to compare children within a family.

    Boys with Klinefelter can have difficulty learning to read, and can sometimes require special help on a one-to-one basis at school. This is possibly related to the particular difficulties that many of them have with short attention span, poor memory and difficulty in keeping things in the right order. 

    These types of problem are not unique to boys with Klinefelter Syndrome, but are found more often in this group of boys than in other children. They can be helped by patience and an appreciation that much repetition may be required in order to retain what has been learnt. In addition, boys with Klinefelter Syndrome may experience problems with the social side of school as they are often quite sensitive. 

    Growth in Childhood and Adolescence 

    Boys with Klinefelter Syndrome often grow faster than usual, especially in the length of their legs. On average, a man with Klinefelter Syndrome will be about 186 cm (6 ft 2 in) tall. If it looks as if a boy is going to be exceptionally tall, his growth can be slowed down by a course of injections. Such treatment is usually organized through a growth specialist, and needs to be commenced in plenty of time, before his height has become a problem. Muscle development in Klinefelter Syndrome is sometimes poor, but this can be improved with exercise.

    Boys can also put on extra fat from about 7 years of age, particularly around the waistline, so it is important to be aware of this possibility and try to maintain a healthy diet and lifestyle to prevent this. 

    Puberty 

    Puberty usually occurs at the normal time and usually progresses normally. However, in some cases the growth of the penis may slow down towards the end of puberty, and the facial, pubic and underarm hair may be quite sparse. This can be treated with supplements of the male hormone, testosterone, which are often given towards the end of puberty.

    A mild degree of breast development (gynecomastia) occurs in about two-thirds of boys with Klinefelter Syndrome. In the majority of boys it resolves without any treatment, but very rarely can persist and cause embarrassment. In such cases, the excess breast tissue can be removed. 

    Fertility 

    Men with Klinefelter Syndrome do not usually produce sperm, and so they have always been considered to be infertile, except in very rare cases. Many males with Klinefelter Syndrome are only diagnosed when they are found to be infertile, having been unaware of any problems before. 

    The lack of sperm does not affect the ability to have sexual intercourse, and the sex life of men with Klinefelter Syndrome is usually normal. Many men marry and couples are able to have children with the help of donor insemination, which can be arranged through a fertility clinic or assisted conception unit. Recently, new techniques of sperm retrieval and fertilisation have succeeded in finding living sperm in a few men with Klinefelter syndrome, and they have been able to become fathers. 

    When Should a Boy with Klinefelter Syndrome be Told about his Condition? 

    Generally it is considered best to begin to explain things in simple terms that the boy can understand from the age of about 10 or 11 years. Statements like "the blood test showed a change in the cells that could mean you grow too tall and put on weight easily" can be used to explain the need for hospital visits and other tests. If testosterone supplements are required, then the explanation can include the fact that it will help the muscles to develop, as well as increase the size of the penis and scrotum. 

    Further information and support is available from: 

    Klinefelter Syndrome Association National Coordinator

    56 Little Yeldham Road

    Little Yeldham, Halstead

    Essex CO9 4QT

    Telephone: 01787 237460 (After 5pm)

    Website: www.ksa-uk.net

    If you need more advice about any aspect of Klinefelter syndrome, you are welcome to contact:

    Cheshire and Merseyside Clinical Genetics Service                                                             Liverpool Women’s Hospital                                   Crown Street, Liverpool L8 7SS

    Telephone: 0151 802 5001 or 5002

    Facsimile:   0151 702 4286

  • Genetic Testing for Lynch Syndrome

    The leaflet is detailed below, or you can download the 'Genetic Testing for Lynch Syndrome' in PDF.

    Introduction

    Cancer is common in the general population with 1 in 2 people being diagnosed with a cancer in their lifetime and most cancer occurs just by chance.  Our suspicions of an inherited explanation for the cancers in a family are raised if the same or similar cancers occur in several family members on the same side of the family, usually across different generations and at a younger age than expected. This is why genetic testing would be offered to a family.

    What Are Genes And Chromosomes?

    Humans are made up of trillions of cells.  At the centre of almost all of your cells is a ball-shaped structure called the nucleus, inside of which are 46 thread-like structures called chromosomes. Chromosomes are long strands of DNA (DeoxyriboNucleic Acid). It is estimated that if a strand of DNA was stretched out, it would be around two meters long, even though the average cell is smaller than a pinhead.

    We have 23 pairs of chromosomes; one of each pair is inherited from your mother and one of each pair from your father. Chromosomes 1-22 are arranged in size order with number 1 being the largest and 22 the smallest. The 23rd pair of chromosomes determines if you are a male or female. Males are XY and females are XX. Chromosomes contain an estimated 20-30,000 pairs of genes that make us who we are. As we have pairs of chromosomes we therefore have pairs of genes

    Genes are often called the blueprint for life because they tell each of your cells what to do and when to do it. For example, some genes determine how tall you will be; some what colour your hair will be; some genes are responsible for maintenance in our bodies and some for our development, and so on. Genes do this by making proteins. In fact, a gene may act by being a ‘recipe’ or a code for making a certain protein. In order for a gene to do the job it is supposed to do, the ‘recipe’ or code needs to be written correctly. If the ‘recipe’ is wrong, the protein is either not made, or is made incorrectly so cannot do the job it is supposed to do.  This is sometimes called a gene alteration, a spelling mistake or a gene mutation.

    What Is Lynch Syndrome?

    Lynch syndrome is a hereditary condition that causes people to have an increased risk of developing certain types of cancer and is caused by a gene alteration.   Lynch syndrome also used to be known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC).                                                                          

    What Are Genes Associated With Lynch Syndrome?

    There are currently 4 genes that we know of that, if they are altered, can be associated with the development of Lynch syndrome. These genes are known as MLH1, MSH2, MSH6 and PMS2. In fact we all have 2 copies each of these genes and they have a very important role to protect certain parts of our body from developing cancer. These genes are called mis-match repair genes and help protect us from developing cancer by detecting and correcting errors that can occur in DNA when cells copy themselves (DNA replication errors). They are like a quality control system that will either repair the mistakes in the DNA or gets rid of the cell with the mistake to stop it being copied anymore.  If there is an alteration in one of our Lynch syndrome genes this quality control system is less effective and the person then has an increased susceptibility to developing cancer. But having an alteration in a Lynch syndrome gene does not mean a person will definitely go on to develop cancer.

    What Are The Main Cancer Risks Associated With Having A Lynch Syndrome Gene Alteration?

    Associated risks

    General Population risk

    With a Lynch syndrome gene alteration

    Bowel cancer

    Men 1 in 14 =~7%

    Women 1 in 19 =~5%

    Men up to an 80% lifetime risk

    Women 40-60% lifetime risk

    (these are the figures quoted if the person has no screening or does not take any other preventative measures)

    Ovarian cancer

    ~1-2% = 1 in 50-100 women

    ~ 10% lifetime risk

    Endometrial cancer

    (womb-lining)

    ~ 1-2.5%

    40-60% lifetime risk

    There may also be a small risk of developing other cancers including kidney (renal) cancer and pancreatic cancer but not enough to warrant routine screening. However, screening for these cancers may be offered if family members have developed these cancers. There is also a low risk of other cancers for which screening is not offered however, it would be important to have a low threshold for seeking medical help for any concerning or persistent symptoms.

    What Can Be Done To Help Manage These Risks?

    For each of the high risk cancers, screening and surgical options are discussed.  Different options are available to men and women, and options can also differ dependent on what age you are.

    For everyone with Lynch syndrome or at 50% risk of having Lynch syndrome

    Bowel Screening.

    Bowel screening involves a FULL colonoscopy every 1-2 years.

    This is an internal examination of the large bowel, also known as colonoscopy. The purpose of a colonoscopy is to look for cancer and polyps.

    Polyps are quite common in the general population, but they are very common in people with Lynch syndrome. Most polyps are harmless and will not cause any trouble. However, the occasional polyp may grow over many years and develop into a cancer 

    It may be possible to prevent a cancer from forming by removing polyps. Removal of polyps is usually carried out during a colonoscopy.

    Helicobacter pylori

    People with Lynch syndrome should also be tested for the presence of a bacterium called Helicobacter pylori (H.pylori) and this can be done through your GP. H.pylori can live in the gut and can lead to chronic gastritis which in turn could lead to an increased risk of stomach cancer for people who carry a Lynch syndrome gene alteration. H.pylori can be detected by a breath test, blood test or stool sample and if found, eradicated with a course of antibiotics.

    Aspirin

    Recent studies have shown that people with Lynch syndrome who take an aspirin a day can significantly reduce the risk of developing bowel cancer and bowel polyps. The exact dosage of aspirin required for maximum effect and the length of time it should be taken has yet to be decided. A further study called CaPP3 has started to try and determine what dose of aspirin should be taken and for how long. Further information regarding this can be found on the following website www.capp3.org.

    (Burn et al 2011, Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial Volume 378, No. 9809, p2081–2087, 17 December 2011)

    PLEASE REMEMBER; Aspirin is a drug that can have serious side effects. It should never be taken without first being reviewed by your GP to make sure there is no reason you should not take it. We are not recommending aspirin usage to anyone without Lynch syndrome.

    Women Also Have The Additional Option Of Gynecological Screening And/ Or Surgery To Help Protect Them Against The Risk Of Developing Ovarian And Endometrial Cancers.

    Ovarian screening and surgery: 

    Ovarian screening involves regular blood tests approximately 3-4 times a year, to measure a marker in the blood called CA125 and also by annual ultrasound scan from the age of 35. 

    Endometrial screening involves an annual transvaginal ultrasound scan and endometrial sampling (sampling of the lining of the womb).

    However, ovarian and endometrial screening often does not reliably inform us of cancers early enough in order for them to be treated effectively. 

    Therefore for women with Lynch syndrome, over the age of 35 and who have completed their families we encourage them to consider having their ovaries, fallopian tubes and womb removed (total hysterectomy and bilateral salpingo-oophorectomy).

    There are clear advantages to having your womb, ovaries and fallopian tubes removed, however they do need to be weighed against the potential disadvantage of being put into an early menopause and the possible need for HRT.  The advantages and disadvantages of HRT could be further discussed with a gynecologist if you chose to go ahead with this process.

    Additional screening offered to men

    For men there is also the option of enrolling on a study called IMPACT. This is a research study that is considering whether or not there is an increased risk of prostate cancer in men. It involves a yearly screen for prostate cancer with a urologist. If you are interested in taking part please ask your genetic counsellor for more information.

    How Lynch Syndrome Gene Alterations Are Passed Down (Inherited) Through Families?

    The way Lynch syndrome gene alterations are inherited is called DOMINANT inheritance. This is caused by an alteration in only one copy of a Lynch syndrome gene. Even though we each have 2 copies of Lynch syndrome genes a normal copy cannot compensate for an altered copy and a person with one altered Lynch syndrome gene has an increased risk of developing cancer.

    If a parent carries an altered Lynch syndrome gene, each of their children has a 50%, or 1 in 2 chance of having inherited the altered gene and therefore having an increased risk of developing cancer. For each child, regardless of their sex the risk is the same = 50:50

    If I Undergo Testing For A Lynch Syndrome Gene Alteration What Will My Results Show?

    Your results will show one of 3 things:

    • A gene alteration is identified in your sample that is known to be disease causing (pathogenic). This is highly likely to be the reason for the cancers in the family. If you have had a cancer this is called diagnostic testing. It also means you remain at risk of developing other cancers associated with having a Lynch syndrome gene alteration.  Finding a gene alteration allows other family members to be offered predictive testing. Predictive testing is offered to family members who are known to be at risk of inheriting a gene alteration that has been identified in the family but are currently well. Predictive testing is usually offered over a series of appointments to allow the opportunity to consider options and choices with time for reflection in-between. How many appointments a person requires varies considerably from person to person and is negotiated on an individual basis with your genetic counsellor team. The overall aim of the predictive testing process is to help prepare a person for their results whatever they are.
    • No gene alteration is identified. This does not mean there is not an inherited genetic explanation for the cancers in the family but it may be that within the confines of current technology we have been unable to detect a gene alteration or, that there may be an alteration in a gene that we do not yet know about and, therefore, cannot test for. Regardless of the results of any genetic testing we may still make screening recommendations for family members based on the family history to help protect their health.
    • A gene change has been found but we are not sure if it is significant or not. This is also sometimes called an unclassified variant (UV) or a variant of unknown significance (VUS). Finding this may mean we have to undertake more testing in the family or that we may need to look at the UV again sometime in the future to see if any further information about it is available. This will be discussed with you in more detail should this be the case.

    *NB: The finding of a pathogenic (disease causing) gene alteration is based on current knowledge. Very occasionally, new information in the future may mean that our understanding of the significance of a specific gene alteration may change.*

    What Are The Issues To Think About When Deciding Whether Or Not To Go Ahead With Genetic Testing?

    A genetic test can establish whether you have an alteration in a gene which could affect your health.

    It can be difficult to make a decision about whether or not to have a genetic test. We all have gene alterations and many of these do not affect our health. It is still quite unusual for a person to know they have an alteration in a specific gene.

    There are reasons for and against having a genetic test. Within one family, relatives often have different views. You should try to make your own decision, without feeling pressured from relatives or other influences.

    You will have plenty of opportunity to talk through the issues surrounding the test with the genetic counsellor or doctor. Some of the things people may consider include:

    • Do I need to tell people I am considering genetic testing?

    It is entirely up to you whether or not you choose to tell anyone you are going ahead with genetic testing. It is often useful to have someone to accompany you to your appointments so that you have another ‘set of ears’ to hear the information and discussions that you have had. They can also be useful as a support for any discussions away from the appointment and should be someone you trust. People often choose this to be their partner, a close friend or another family member. However, if you choose to bring a family member it is important to remember the discussions you have in clinic are likely to have implications for them as well and they may not be prepared for this.  Our experience, however, has demonstrated that families are often aware of the cancers and may already be asking questions about why and so it may be that an opportunity to discuss this within the family could happen quite naturally anyway.

    Other people would rather wait until there is something to know before discussing things with the wider family, whilst other people prefer to discuss things as the process goes along to help prepare the family for any news. There are no right or wrong answers and we are happy to discuss how to involve your family if you wish.

    • Do my family need to know about any results I receive from genetic testing?

    Genetic testing provides information for the individual but also will provide information for the rest of the family. If genetic testing identifies a gene alteration in you we would assume that you had inherited it from either your mother or father. Altered genes can often be passed down through families over generations without being noticed. Therefore, finding a gene alteration in you will have implications for other family members as well. So sharing genetic information in a family is really important. It can provide family members with a real opportunity to protect their health by enrolling in screening programmes to detect cancers as early as possible or even surgical options to help reduce the risk of developing cancer in the first place.

    Sometimes people may think if genetic testing does not show anything then there is nothing to tell anyone. However, knowing what is happening in the family can prevent work being repeated as sometimes lots of family members are asking the same questions. It is also very important to remember that, regardless of the results of any genetic testing, the family history itself may mean family members are at a higher risk of cancer anyway and opportunities to protect their health can be offered to them.

    • How can I share this information?

    On a practical level, you will have this leaflet to share with them and we will also provide a letter after your clinic appointment detailing any other issues discussed.

    If a gene alteration is found we will provide you with a ‘relative’s letter’ detailing that a gene alteration has been identified in the family, that they are at risk and how to access testing. We will also guide you as to whom the letter should be passed on to.

    On an emotional level, telling family members may be more difficult. You may be worried about upsetting them or have trouble deciding when the right time is. There really is no right or wrong answer to this but it is really useful to think about this before you get your test results and we are more than happy to discuss this with you further. 

    • I won’t tell my children, it will only worry them?

    As parents, we want to protect our children from things that we believe can harm them and sometimes this means that we try and ‘hide’ things we think may be difficult for them to cope with. However, we tend to underestimate what children have already picked up on and they are often aware of something going on anyway. They may have noticed letters from the hospital or overheard conversations, they may also pick up cues from adults that they should not ask any questions.

    Children in this situation may imagine something really awful is going on, often much worse than the reality, and may even believe it is something bad they have done.

    Children value being included and are helped by adults who are honest and direct with communication. It is not always easy but children often cope a lot better than we give them credit for.

    Our experience has also shown us that the parents of adult children often do the same. We are happy to talk to you about sharing information with your children during your appointment.

    • Who else should I tell?

    That is entirely up to you. There is generally no obligation to tell your employer but it might be useful if you anticipate you may need time off work to have screening.

    Having friends to discuss this with is helpful for some people but it is important to be aware that people may have differences of opinion that could be in conflict with any decisions you have made.

    However, for the majority of people, having discussions with other people is helpful and supportive.

    • What happens if I choose to go ahead and have a test?

    After you have discussed what genetic testing could mean for you, you may decide to go ahead with testing. We will ask you to sign a consent form and we will take a blood sample from you.

    The laboratory team will then search through the Lynch syndrome genes in your blood sample to see if the code in any of these genes differs from that of a normal gene. The Lynch syndrome genes are large and can take a long time to be looked through. We would expect results to be ready in approximately 3-4 months but please remember sometimes it can be more and sometimes less.

    You can discuss with your genetic counsellor or doctor how you wish to receive your results. Some people want their results by letter or over the telephone with the opportunity of a follow-up appointment to discuss any findings, whereas others prefer to come into clinic to have the opportunity to discuss the implications of any findings and next steps. This is entirely up to you and will be discussed during your appointment.

    What are the Issues to think about when deciding whether or not to go ahead with genetic testing.

    A genetic test can establish whether you have an alteration in a gene which could affect your health.

    It can be difficult to make a decision about whether or not to have a genetic test. We all have gene alterations and many of these do not affect our health. It is still quite unusual for a person to know they have an alteration in a specific gene.

    There are reasons for and against having a genetic test. Within one family, relatives often have different views. You should try to make your own decision, without feeling pressured from relatives or other influences.

    You will have plenty of opportunity to talk through the issues surrounding the test with the genetic counsellor or doctor. Some of the things people may consider include:  

    IF, FOR SOME REASON YOU, HAVE NOT RECIEVED YOUR RESULTS WITHIN 3-4 MONTHS AS EXPECTED PLEASE CALL THE CLINICAL GENETICS DEPARTMENT ON 0151 802 5008. Please remember to have your G number and W number handy for this call so we can quickly and correctly identify you.

    • What happens if I choose not to go ahead with having a test?
    • We will make screening recommendations for your relatives based on the family history of cancer.
    • We will not be able to offer predictive testing to your relatives.

    Attending clinical genetics does not oblige you to go ahead with testing and, if you do go ahead and change your mind about receiving your results, you can do so until you are ready.

    Other Factors to Consider

    Insurance and Genetics

    For some types of insurance it is necessary to provide medical information, including genetic information, to the insurers in order for them to set up your policy and work out your premiums. The types of policy that require a medical history or genetic test are likely to be, life cover, critical illness insurance and income protection insurance.

    We would suggest that if yourself or family members are considering taking out new insurance policies in the future that consideration be given to the possible affect genetic test results could have on the ability to gain insurance or the premiums charged. Genetic Test results do not affect insurance policies already in place.

    The Association of British Insurers (ABI) has a Code of Practice ‘The Concordat and Moratorium on Genetic and Insurance’.

    • Insurance companies cannot ask for the Predictive Genetic Test results of individuals or family members (unless for Huntington Disease over £500,000). A Predictive Genetic Test is where an individual has a family member with a genetic condition, but who personally has no symptoms, signs or abnormal medical tests consistent with the condition at time of testing.
    • If a family member has been diagnosed with a genetic condition based on a Diagnostic Genetic Test then you or family members will need to mention this when asked to provide your family’s medical history. In many cases Diagnostic Genetic Testing is used to confirm a diagnosis when a particular condition is suspected because of symptoms, signs or abnormal non-genetic tests including unusual findings on a routine blood test or other test.

    Sources of Further Information Include

    The Association of British Insurers Genetics Frequently Asked Question’s https://www.abi.org.uk/products-and-issues/topics-and-issues/genetics/genetics-faqs/

    Genetic Alliance UK (Charity) Genetics & Insurance http://www.geneticalliance.org.uk/information/living-with-a-genetic-condition/insurance-and-genetic-conditions/

     

    We hope you find this leaflet useful and please do not hesitate to discuss any of the issues identified in this leaflet with the genetics practitioner that is looking after you.

     

    Useful websites

    Genetic Alliance UK www.geneticalliance.org.uk

    Cancer research group UK (CRUK) www.cruk.org.uk

    National Institute for Health Care and Excellence (NICE) www.nice.org.uk/Guidance/CG41

     

    All images in this leaflet were provided by NHS National Genetics and Genomics Education Centre

  • Predictive Testing for Huntington’s disease

    The leaflet is detailed below, or you can download the 'Predictive Testing for Huntington’s disease' in PDF.

    Testing For the Huntington Disease Gene

    This leaflet will explain how our department approaches predictive testing for Huntington disease. A predictive test is a test which predicts whether or not a person, who has a family history of Huntington disease, but has no symptoms themselves, will actually go on to develop the disease in the future.

    The Process for Predictive Testing

    The process for predictive testing was developed with the help of the Huntington’s disease Association (see below for contact details), and is used by genetic centres throughout the United Kingdom.  It involves a series of appointments.

    At your appointments you will meet with two members of the clinical team. We make every effort to ensure that you will see the same members of clinical staff at all of your appointments. We welcome and encourage you to bring someone with you for help and support.

    What Does It Involve?

    1st Pre-Test Appointment

    No Testing Is Done At This Appointment

    We need to know about your family history of Huntington’s disease so that, wherever possible, we can ensure that we are testing for the right condition.  It also gives us the chance to explain the signs and symptoms of Huntington’s disease, how it is passed on through families, and what your chances are of having the faulty Huntington’s gene.  We also need to discuss whether doing a test on you could have implications for other members of your family.

    We will explain the test to you, how it works, and what the limitations are.  We will discuss the effect a "good news" or "bad news" result may have on you and your family.

    If you still wish to be tested, we will arrange a further appointment for you.  Some people, however, decide that they do not wish to go ahead and have the test at this time. You are free to stop at any time during the testing programme, should you want to.

    2nd Pre-Test Appointment

    The aim of this appointment is to look at the advantages and disadvantages of knowing for certain whether or not you are going to develop Huntington disease. Once we have given you the result you can never go back, so it is important that you are clear that you want to know before we test you.

    There will be an agreed time period before the next appointment which gives you time to think and talk through the issues raised. You may also have practical things which will need to be sorted out before your test (such as life insurance). These issues will be discussed in detail at this session.

    The Test Appointment

    This appointment gives you the chance to talk through any matters which may have arisen.

    If you decide you want to have the test done, then we usually offer to take the blood sample.

    It takes 4-6 weeks from the blood sample being taken, for the laboratory to process the test and issue a result.

    The Result Appointment

    This appointment is to give you the result of the test in person. We never give out these results over the telephone or in a letter. The date of your result appointment will be agreed with you in advance.

    The staff involved in your appointments will not know the result of your test until shortly before you do. We do this so that you can telephone us at any time before the result appointment without worrying that we know something, but are not telling you.

    We understand that this process may seem very long, but it is the result of much discussion with people who have already been tested and with staff involved in the testing process.

    For more information:

    If you need more advice about any aspect of the predictive testing process for Huntington disease, you are welcome to contact:

    Cheshire and Merseyside Clinical Genetics Service

    Department of Clinical Genetics

    Liverpool Women’s Hospital NHSFT

    Crown Street

    Liverpool

    L8 7SS

    Telephone 0151 802 5001 or 5002

    Further information and support is available from Huntington’s disease Association

    Suite 24

    Liverpool Science Park

    Innovation centre 1

    131 Mount Pleasant

    Liverpool

    L3 5TF

    Telephone 0151 331 5444

    Fax 0151 331 5441

    Email info@hda.org.uk

    Website www.hda.org.uk

  • Recessive Inheritance

    The leaflet is detailed below, or you can download the 'Recessive Inheritance' in PDF.

    What Are Genes?

    Genes are the unique set of instructions inside our bodies which make each of us an individual. There are many thousands of different genes, each carrying a different instruction. If a gene is altered, it can cause a genetic condition or disease. This gene alteration is sometimes known as a mutation.

    We have two copies of each gene. One copy is inherited from each of our parents. When we have children, we pass on only one copy of each of our genes.

    What Does Recessive Inheritance Mean?

    Some conditions are inherited in a recessive way. In recessive conditions, individuals who have only one altered copy of a gene are completely healthy. They are known as carriers, because they carry one altered copy of a gene. Their normal copy of the gene keeps them healthy and compensates for the altered copy of the gene.

    Having Children

    If both healthy parents carry the same altered recessive gene, then each child they have has a 25% (1 in 4) risk of inheriting the altered gene from both parents and therefore being affected. For each child, regardless of their sex, the risk is the same = 25%.

    Children of couples who are both carriers of the same altered recessive gene have a 50% (1 in 2) chance of inheriting one copy of the altered gene from one of their parents. If this happens, they are healthy carriers themselves. There is also a 25% (1 in 4) chance that a child of a carrier couple will inherit two normal copies of the gene. These children will be completely normal.

    If only one parent is a carrier of the altered gene, then each of their children has a 50% chance of being a healthy carrier, but will not be affected.

    Parents who are closely related to each other, such as first cousins, are more likely to have children with recessive conditions

    If you need more advice about any aspect of Recessive Inheritance, you are welcome to contact:

    Cheshire and Merseyside Clinical Genetics Service

    Liverpool Women’s Hospital NHS Foundation Trust

    Crown Street

    Liverpool

    L8 7SS

    Telephone 0151 802 5001 or 5002

    Facsimile: 0151 702 4283 or 4286

  • Tissue Studies for Lynch Syndrome

    The leaflet is detailed below, or you can download the 'Tissue Studies for Lynch Syndrome' in PDF.

    Introduction

    Lynch syndrome is a hereditary condition that causes people to have an increased risk of developing certain types of cancer.  Men and women who have Lynch syndrome have an increased risk of developing colorectal cancer, which is a cancer of the large bowel (colon) and rectum. Women who have Lynch syndrome also have an increased risk of developing cancer of the womb (uterus) and ovaries.

    How Common Is Colorectal, Womb and Ovarian Cancer in the General Population?

    In the UK colorectal cancer affects 1in 15 men and 1 in 19 women during their lifetime.

    Approximately 1 in 52 women will develop ovarian cancer and 1 in 41 women will develop cancer of the uterus (Cancer research UK statistics: 2012).

    How Common Is Lynch Syndrome

    Lynch Syndrome is rare and only approximately 1 in 20 people with bowel cancer will have Lynch Syndrome.

    Why Should I Have This Test?

    Finding out your cancer/bowel polyps are due to Lynch Syndrome will mean we can test other family members to see if they also have Lynch Syndrome. We can then offer screening and/or surgery to you and family members with Lynch Syndrome to detect cancers at a very early stage or even help prevent certain cancers developing in the first place.

    What Causes Lynch Syndrome?

    Lynch Syndrome is caused by an alteration (spelling mistake/error) in one of 4 genes. These genes are called MLH1, MSH2, MSH6 and PMS2.                                                                 

    What do Tissue Studies involve?

    Tissue studies are tests on samples of a cancer or polyp material removed during surgery or bowel screening.  These tests may help to identify if the cancers and/or bowel polyps which have occurred in the family are likely to be due Lynch Syndrome

    What Test Is Performed?

    The test we would like to perform is called Immunohistochemistry (IHC) testing.

    IHC testing checks if the 4 genes associated with Lynch Syndrome are working properly. Genes make proteins and IHC tests to see if the MLH1, MSH2, MSH6 and PMS2 proteins are present in your tumor sample. 

    What Happens If Any Abnormalities Are Identified?

    If testing shows that one or more of the proteins is missing this could indicate that the tumor/polyp was due to Lynch Syndrome. However, it is important to remember that further testing will be needed to confirm this.  You will be offered a follow-up appointment to discuss in more detail should this be the case.

    What Happens If NO Abnormalities Are Identified?

    If the IHC test is normal it is much less likely that bowel cancer and the cancers in the family are due to Lynch syndrome.

    In these circumstances screening advice will be offered to family members in relation to the family history of cancer

    What about the Results?

    The test is complicated and the results can take up to six months.  We will contact the person who has consented to the tests to give them the results.  We will also update our advice about screening and whether any further testing could be useful.  Someone from the genetics team will contact you to discuss this further if appropriate.

    What If No Tissue Is Available?

    Sometimes we cannot get a tissue sample. However, it may be possible to get one from another relative who has had a related cancer.  If we cannot get tissue from any relatives, we will give advice based on the information we already have. 

    What Do I Need To Do?

    To go ahead with these tissue studies we need permission from the individual who has had cancer.  If this individual has passed away, a relative can give permission on their behalf.  If they passed away after September 2006, consent is needed from one person in the hierarchy of qualifying relationships and should be obtained from the person ranked highest. 

    1. Spouse or partner (including civil or same sex partner) The HT Act states that, for these purposes, a person is another person's partner if the two of them (whether of different sexes or the same sex) live as partners in an enduring family relationship.
    2. Parent or child (in this context a child may be of any age and means a biological or adopted child)
    3. Brother or sister
    4. Grandparent or grandchild
    5. Niece or nephew
    6. Stepfather or stepmother
    7. Half-brother or half-sister
    8. Friend of long standing.

    If you want us to go ahead with these tissue tests, you need to complete and return the appropriate consent form.  If you do not have a consent form and would like one, please contact the department. If you are consenting to tests on tissue of a deceased relative we would encourage you to discuss the decision with other family members.

    If you do not want us to go ahead with the tests please let us know so we can provide advice based on the family history you have given without delay.

    If you need more advice about any aspect of bowel cancer, you are welcome to contact:

    Cheshire and Merseyside Clinical Genetics Service

    Liverpool Women’s Hospital

    Crown Street

    Liverpool, L8 7SS

    Telephone 0151 802 5001 or 5002

    Facsimile: 0151 702 4286 

    Further information

    Liverpool Women’s Hospital Lynch syndrome information leaflet

    http://www.cancerresearchuk.org/

    http://www.macmillan.org.uk/Home.aspx

    Human Tissue Authority (HTA) Code of Practice – 1 Consent

    Version 14.0 Updated: July 2014 Scheduled review date: July 2016 www.hta.gov.uk

    Consent and confidentiality in clinical genetic practice: Guidance on genetic testing and shearing genetic information A report of the Joint Committee on Medical Genetics  Royal College of Physicians and Royal College of Pathologists 2011

     http://www.Lynch-syndrome-uk.org

     https://www.bowelcanceruk.org.uk/

    https://www.nhs.uk/conditions/Cancer-of-the-colon-rectum-or-bowel

    https://www.genomicseducation.hee.nhs.uk/resources/genetic-conditions-factsheets/item/81-lynch-syndrome

  • X-Linked Inheritance

    The leaflet is detailed below, or you can download the 'X-Linked Inheritance' in PDF.

    What Are Genes And Chromosomes?

    Genes are the unique set of instructions inside our bodies which make each of us an individual. There are many thousands of different genes, each carrying a different instruction. If a gene is altered, it can cause a genetic condition or disease. This gene alteration is sometimes known as a mutation.

    We have two copies of each gene. One copy is inherited from each of our parents. When we have children, we pass on only one copy of each of our genes. Genes lie on tiny structures called chromosomes. Women have two X chromosomes and men have one X and one Y chromosome. The Y chromosome is much smaller than the X chromosome and contains fewer genes.

    What Does X-Linked Inheritance Mean?

    X-linked conditions occur when an altered gene is located on the X chromosome.

    If a woman has an altered gene on one of her two X chromosomes, then she will be a healthy carrier. She is healthy because she has a second normal copy of the gene on her other X chromosome.

    If a man has an altered gene on his X chromosome, then he will be affected as he has only one X chromosome.

    Having Children

    Carrier Females - If a woman carrier has a boy, there is a 50% (1 in 2) risk that the boy will be affected by a condition caused by the altered gene that she carries on her X chromosome.

    If a woman carrier has a girl, there is a 50% (1 in 2) risk that the girl will inherit the X chromosome altered gene, If this happens she will most likely be a healthy carrier, like her mother.

    Affected Males (diagram B) - When men who are affected by X-linked conditions have children, all of their daughters inherit the altered gene on their X chromosome. These daughters will all be carriers.

    Men do not pass on their X chromosomes to their sons. Therefore, all the sons of men with X-linked conditions are completely unaffected (diagram B).

    Note - Sometimes boys are born with X-linked conditions even though their mothers are not carriers. When this happens, it is particularly important to get specialist advice about future pregnancies.

    If you need more advice about any aspect of X-linked Inheritance, you are welcome to contact:

    Cheshire and Merseyside Clinical Genetics Service Liverpool Women’s Hospital

    Crown Street

    Liverpool, L8 7SS

    Telephone 0151 802 5001 or 5002

    Facsimile: 0151 802 5096

  • Microarray Leaflet – Fetal Loss

    The leaflet is detailed below, or you can download the 'Microarray Leaflet – Fetal Loss' in PDF.

    Introduction

    Losing a baby is understandably a difficult time. Many people in this situation have questions about why their baby had problems. Your doctor has decided to order a test called microarray to investigate the problems which were identified in your baby. This leaflet aims to explain what this test involves and the possible outcomes.

    What are Chromosomes and Genes?

    Genes are tiny 'packages' of vital information made from DNA, which influence our growth and development.

    Each person has about 20,000 pairs of genes. They work like instructions that determine things like the colour of our eyes, how many fingers and toes we have and how tall or short we are. Genes are so small that they cannot be seen, even under a powerful microscope. They are arranged along threadlike strands, rather like beads along a string. These strands are called chromosomes, and are inside most of the cells in our body.

    Most cells in a person's body contain 23 pairs of chromosomes (46 in total), which can be seen down the microscope. To help tell which chromosome is which, each pair has been given a number. Pair number 1 is the largest; pair number 2 is the next largest and so on right down to pair number 22 which is the smallest. The remaining two chromosomes (X and Y) are called the sex chromosomes and they determine whether a person is male (XY) or female (XX).

    Everyone has some small variations on their chromosomes but not all of these cause problems. However, some people who have certain changes in the number or structure of their chromosomes may have a variety of problems, including heart defects, abnormalities of the fingers or toes and many others. Importantly, everyone has some small changes on their chromosomes, not all of them cause problems.

    Chromosome tests

    Karyotype – Chromosomes cannot be seen by the naked eye but can be seen under powerful microscopes. This test may have already been performed on a sample from your baby and you may have been given a “normal” result for this test. This means that there are no obvious large pieces of chromosome material missing or extra and they are arranged in the right order.

    Microarray – This test uses new techniques to look at the chromosomes in much finer detail and can pick up if much smaller pieces of chromosome material are missing (deletion) or extra (duplication) than can be seen down a microscope.

    What happens now?

    A sample of DNA from your baby will be analysed in our laboratory by microarray. Results will take approximately 12 weeks and the doctor will contact you once the results are received.

    Results  

    There are three possible outcomes from the results of microarray.

    • The chromosomes may appear entirely normal. A normal microarray test does not rule out all genetic conditions as there may still be changes in individual genes, which cannot be detected by a microarray test
    • The test may reveal a change which is highly likely to account for the problems which were identified in your baby. If a change is identified then you may be referred to the clinical genetics department to discuss this further.
    • We could identify a change that we do not kno w the significance of – in other words, we do not know if it may be the cause of your baby’s problems or not. In this case we will ask for samples from both parents in order to identify if you have the same change as your baby had in their DNA. If one of you carries the same change, it is likely that the change is simply part of normal variation.

    There is also a very small chance that we could pick up something unrelated to your baby’s problems which may have implications for the family’s future health e.g. early onset cancer or heart disease. We would inform you of this result.

  • Microarray Leaflet for Parents

    The leaflet is detailed below, or you can download the 'Microarray Leaflet for Parents' in PDF.

    Introduction

    Your child’s doctor has decided to order a test called microarray-based comparative genomic hybridisation (microarray). This leaflet aims to explain what this test involves and the possible outcomes. 

    What are Chromosomes and Genes?

    Each person has about 20,000 pairs of genes. They work like instructions that determine things such as the colour of our eyes, how many fingers and toes we have and how tall or short we are. Genes are so small that they cannot be seen, even under a powerful microscope. They are arranged along strands, rather like beads along a string. These strands are called chromosomes, and are inside most of the cells in our body.

    Most cells in a person's body contain 23 pairs of chromosomes (46 in total), which can be seen down the microscope. To help tell which chromosome is which, each pair has been given a number. Pair number 1 is the largest; pair number 2 is the next largest and so on right down to pair number 22 which is the smallest. The remaining two chromosomes (X and Y) are called the sex chromosomes and they determine whether a person is male (XY) or female (XX).

    Everyone has some small variations on their chromosomes but not all of these cause problems. However, some people who have certain changes in the number or structure of their chromosomes may have a variety of problems, including developmental delay, learning and behavioural problems, heart defects, abnormalities of the fingers or toes and many others. Importantly, everyone has some small changes on their chromosomes, not all of them cause problems.  

    Chromosome tests

    Karyotype – Chromosomes cannot be seen by the naked eye but can be seen under powerful microscopes. Your child may have already had this test done and had a “normal” result. This means that there are no obvious large pieces of chromosome material missing or extra and they are arranged in the right order.

    Microarray – This test uses new techniques to look at the chromosomes in much finer detail and can pick if much smaller pieces of chromosome material are missing (deletion) or extra (duplication) than can be seen down a microscope.

    What happens now?

    A blood sample will be taken from your child and sent to our laboratory for microarray. Results will take approximately 12 weeks and the doctor will contact you once the results are received. If the laboratory has a sample of DNA stored from a previous genetic test that your child has had it may be possible to test this DNA sample. However a new blood sample may be required.

    Results

    There are three possible outcomes from the results of microarray.

    • The chromosomes may appear entirely normal. A normal microarray test does not rule out all genetic conditions as there may still be changes in individual genes, which cannot be detected by a microarray test.
    • The test may reveal a change which is highly likely to account for the problems that your child has. If we identify such a change then we can see you in clinic again to discuss this.
    • We could identify a change that we do not know the significance of – in other words, we do not know if it may be the cause of your child’s problems or not. In this case we will ask for samples from both parents in order to identify if you have the same change as your child has in their DNA. If one of you carries the same change, it is likely that the change is simply part of normal variation.

    There is also a very small chance that we could pick up something unrelated to your child’s current problems which may have implications for their/the family’s future health e.g. early onset cancer or heart disease. We would inform you of this result.

  • Prenatal Array CGH

    The leaflet is detailed below, or you can download the 'Prenatal Array CGH' in PDF.

    Prenatal Array CGH (Comparative Genomic Hybridisation): Information for Patients

    This leaflet provides information about prenatal array CGH. Please read it before you agree to have the test.

    What Is Array CGH?

    Array CGH is a test used to detect chromosome changes which are too small to be seen by standard chromosome tests

    What Are Chromosomes?

    Chromosomes are the structures in each of the body’s cells that carry the genetic information (DNA) that tells the body how to develop and function. Each cell in the body has 46 chromosomes in 23 pairs. We inherit one member of each chromosome pair from each parent. Girls/women usually have two X chromosomes (XX) and boys/men usually have an X and a Y chromosome (XY). The other chromosome pairs are numbered from 1 to 22. Having too much or too little chromosomal material may cause significant problems with physical and intellectual development.

    Why Has An Array CGH Test Been Offered To You?

    In order to diagnose a chromosome abnormality it is necessary to examine the baby’s cells obtained by an invasive test; either a CVS or an amniocentesis. The first test usually offered (known as QF-PCR) involves checking your baby’s chromosomes for the most common syndromes such as Down’s syndrome (trisomy 21), Edward’s syndrome (trisomy 18) and Patau syndrome (trisomy 13). These results are usually available after 48 hours.

    If the result of the QF-PCR test is normal then a second test known as array CGH is offered when, for example, an ultrasound scan has shown structural abnormalities or a raised nuchal translucency, or if you have previously had a baby with a chromosome abnormality. These results are usually available in about two weeks

    What Are The Advantages Of Array CGH?

    The main advantage of array CGH is that it can detect very small chromosome changes which cannot be seen otherwise. These changes are called micro deletions (tiny pieces of missing chromosome) and micro duplications (tiny pieces of extra chromosome). If these changes are found it may allow more precise information to be given to you about your baby.

    What Are The Disadvantages And Limitations Of Array CGH?

    Array CGH does not detect all chromosome changes as some are still too small to be identified. Some conditions are caused by changes in individual genes which array CGH cannot detect.

    Sometimes results can be difficult to interpret unless a blood sample from both parents is available for comparison.

    Array CGH may also detect changes called ‘variants of unknown significance’ (VUS). This means there is not yet enough information available to know if these are significant or not. Where there is uncertainty, these variants may not be reported. This is because a VUS may not provide reliable information about how your baby will develop, or how the pregnancy will progress.

    What Else May Array CGH Tell Us?

    Array CGH may occasionally identify a chromosome change which is not related to the reason for the test being done but which may have implications for the future health of your baby and possibly for other family members. This is called a secondary or incidental finding. For example, it may show your baby will have an increased risk of cancer later on in life. This chromosome change may have been inherited from a healthy parent but may not. Carriers of these types of chromosome changes could benefit from screening. This may not be relevant at the time of the pregnancy but could be discussed at a later date.

    What Are The Possible Outcomes Of An Array CGH Test?

    • No clinically significant chromosome change is detected.

    Which means the test did not show a change related to the reasons for testing.

    • A clinically significant chromosome change is detected which is related to the reasons for testing. This will be discussed in more detail with you.
    • A variant of unknown significance (VUS)

    These are usually not reported as their significance is unclear.

    • A secondary/incidental finding not related to the reason for the test

    Further Questions

    If you have more questions about array CGH please ask the doctors or midwives in the Fetal Medicine Unit or your genetics clinician.

    Other Services

    UNIQUE

    UNIQUE offers support and information for parents of babies diagnosed with rare chromosome and gene disorders. Tel: 01883723356 Web: www.rarechromo.org

    Antenatal Results and Choices (ARC)

    Offers information and support to parents before, during and after antenatal screening.

    Tel: 0845 077 2290 / 020 7713 7486 Web: www.arc-uk.org

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