Clinical Genetics Leaflets

The leaflet is detailed below, or you can download the 'BRCA1 Gene Alteration' in PDF.

The BRCA1 gene

BRCA1 is a gene that we all have. Having an alteration in the BRCA1 gene can increase the chance of   breast, ovarian, prostate, and pancreatic cancer. The chance is affected by:

• Age
• Sex
• Family history
• Other factors e.g., lifestyle, hormonal history.

Chance of Cancer and Management Options

In the UK, breast cancer affects approximately 1 in 7* women and people assigned female at birth during their lifetime. Most of these people are aged over 60. It is very rare for men and people assigned male at birth to develop breast cancer.

* Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960

If a genetic test shows that you have BRCA1 gene alteration, you will have an increased chance of developing certain types of cancer. The chances for each type of cancer are shown in the table below^.   

Anyone with a BRCA1 gene alteration can take part in research.

NB: Test results are reported based on current knowledge. Very occasionally, new information in the future may mean that our understanding of the significance of a specific gene variant may change.

** The risk in women and people assigned female at birth is no higher than the national average

^ Data from UK Cancer Genetics Group BRCA1 Germline Pathogenic Variant Carriers Management Guidelines for Healthcare Professionals v2 updated 31.03.2023

How is the BRCA1 gene alteration inherited?

We all have two copies of every gene including BRCA1. One copy is inherited from each of our parents. If we have children, we only pass on one copy of each of our genes in each pregnancy.

If an individual with an BRCA1 gene alteration has children, there is a 50% (1 in 2) chance their BRCA1 gene alteration could be passed on. There is also a 50% (1 in 2) chance their children could inherit the typical copy of the parent’s BRCA1 gene. 

What can I do to help improve my health?

We encourage people to not smoke, to be a healthy weight, to eat less red and processed meat, to not drink too much alcohol and to exercise regularly. Doing these things can all help to reduce the chance of developing many types of cancer.

You should also report any changes in your breasts to your GP. If you have a personal or family history of breast cancer you should discuss this with your GP before taking hormone replacement therapy.

Are there any research studies for BRCA1?

The Epidemiological Study of Familial Breast Cancer (EMBRACE) aims to identify risk factors contributing to the development of cancer in people with an inherited cancer gene alteration. If you are interested in discussing the possibility of participating in any research studies, please ask your Genetic Counsellor or Doctor.

This leaflet is for people who have appointments at

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5003 or 5008             

Email: lwft.clingen@nhs.net

 

 

 

 

 

 

                                                                              

 

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 contains a disease-causing (pathogenic) alteration, it can cause people to have an increased chance of developing a genetic condition. A gene alteration is sometimes known as a gene variant.

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 through 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. This means having a pathogenic alteration in one copy of the gene is enough to put individuals at an increased chance of developing the condition.

Having children

If a parent carries an altered gene for a dominant condition, each of their children has a 50%, or 1 in 2 chance 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.

 

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

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

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008  

Email: lwft.clingen@nhs.net           

 

 

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 Ileo-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

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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 in the UK, with 1 in 2* people being diagnosed with some form of cancer during their lifetime. Most cancers are due to chance and/or environmental factors. For example, we know that the chance of developing cancer increases as we get older, and that lifestyle factors such as smoking, drinking alcohol and being overweight increase the chance of developing many cancers. Some cancers occur due to inherited genetic factors. We are more suspicious of there being an inherited cause for the cancers in a family if the same or related cancers occur across multiple generations, are diagnosed at younger than expected ages, with more people developing cancer than we would expect by chance.

*Cancer research UK (2015) Estimated Lifetime Risk of being diagnosed, people born after 1960.

What are genes and chromosomes?

Humans are made up of trillions of cells.  At the centre of almost all of our 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.

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

Image Source: https://cpmc.coriell.org

We have 23 pairs of chromosomes and one of each pair is inherited from each parent. Chromosomes contain an estimated 20-30,000 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. 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 variant, a spelling mistake or a mutation.

Pic3

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

What is Lynch syndrome?

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

There are currently 4 mismatch repair genes that we know of that act like a quality control system; MLH1, MSH2, MSH6 and PMS2. They help protect us from developing cancer by detecting and correcting errors that can occur in DNA when cells copy themselves (DNA replication errors). Having a pathogenic variant in one of these genes means that the quality control system is less effective, and the person has Lynch syndrome and so is more likely to develop certain types of cancer. Having Lynch syndrome does not mean a person will definitely go on to develop cancer.

Having Lynch syndrome causes a high chance of developing bowel cancer. People with Lynch syndrome who were assigned female at birth also have a high chance of endometrial (womb) cancer and often a high chance of ovarian cancer, depending on the particular gene in which the pathogenic variant is found. If a gene variant is found, gene-specific cancer risks can be provided. There may also be a slightly increased chance of developing other cancers including kidney (renal) cancer and pancreatic cancer, but not enough to warrant routine screening unless there is a family history.

Additional screening and/or risk-reducing measures may be advised depending on individual risks. Options will be discussed in detail if genetic testing shows you have Lynch syndrome.

How is Lynch syndrome passed down (inherited) through families?

Lynch syndrome is inherited in an autosomal dominant inheritance pattern. We have two copies of each of the mismatch repair genes and if one copy has a variant then this means the person has less protection against developing certain types of cancer and they have Lynch syndrome. Each time someone with Lynch syndrome has a child, there is a 50% chance of passing on the working copy of the gene and a 50% chance of instead passing on the gene variant causing Lynch syndrome. Someone with Lynch syndrome has usually inherited this from one of their parents.

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

What might my genetic test results show?

Your results will show one of 3 things:

1. A gene variant is identified in your DNA 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 have an increased chance of developing other cancers associated with Lynch syndrome. Predictive genetic testing can be offered to family members who may have inherited the family-specific gene variant
2. No gene variants are identified. This reduces the chance that you have Lynch syndrome but does not completely rule out there being an inherited genetic explanation for the cancers in the family. It may be that within the confines of current technology we have been unable to detect a gene variant, or you may have a variant in a gene we do not yet know about and therefore cannot test for. Taking these results into account, we may still make screening recommendations for family members based on the family history to help protect their health.
3. A gene variant 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: Test results are reported based on current knowledge. Very occasionally, new information in the future may mean that our understanding of the significance of a specific gene variant 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 a variant 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. There are reasons for and against having a genetic test. Within a 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 person to help process 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 may have implications for them as well and they may not be prepared for this.  Our experience, however, has demonstrated that relatives are often aware of the cancers in the family and may already have questions, and so it may be that an opportunity to discuss this within the family could happen quite naturally anyway.

 

Some 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 could also provide information for the rest of the family. If genetic testing identifies a gene variant, we would assume that you had inherited it from one of your parents. Lynch syndrome can often be passed down through families over generations without being detected. Sharing genetic information in a family is really important because it provides family members with the 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 tests being repeated as sometimes lots of family members are asking the same questions. It is also very important to remember that, even if we do not find that you have Lynch syndrome, the family history itself may mean family members are at a higher risk of cancer 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 you are found to have Lynch syndrome, we will provide you with a ’Dear Family Member Letter’ detailing that a gene variant 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 happy to discuss this with you further. 

 

• Should I tell my children?

 

Parents naturally want to protect children from things that can harm them and sometimes this means that parents try and hide things they think may be difficult for their children 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 and may instead not feel able to share worries.

 

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 you will have a blood sample taken. The laboratory team will then search through the Lynch syndrome genes in your DNA 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.

 

IF, FOR SOME REASON YOU, HAVE NOT RECIEVED YOUR RESULTS WITHIN 3-4 MONTHS AS EXPECTED PLEASE CALL THE LIVERPOOL CENTRE FOR GENOMIC MEDICINE 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.

 

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 on insurance and genetics:

The Association of British Insurers Genetics Frequently Asked Questions 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:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008              Email: lwft.clingen@nhs.net

 

 

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

Testing for the Huntington’s Disease gene

This leaflet will explain how our department approaches predictive testing for Huntington’s disease. A predictive test is a test which predicts whether or not a person, who has a family history of Huntington’s 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.  Appointments are usually carried out face to face, however video appointments can also be arranged.

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. Occasionally, we have trainee clinicians observing clinics, however if you do not wish for anyone to observe your appointment then please let your clinician know. We welcome and encourage you to bring someone with you for help and support.

What does it involve?

1^st 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.

2^nd 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’s 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 2 - 3 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.

You do not have to convince us to test you

It is your decision whether to have the test. We are here to give you information to help you think through the issues involved, and to give you help and support.

Once again, you can withdraw from the testing process at any time.

For more information:

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

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

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

 

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

 

 

 

The leaflet is detailed below, or you can download the 'Recessive Inheritance' leaflet 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 contains a disease-causing (pathogenic) alteration, it can cause people to have an increased chance of developing a genetic condition. A gene alteration is sometimes known as a gene variant.

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 of the condition because they carry one altered copy of a gene. Their typical copy of the gene keeps them healthy and compensates for the altered copy of the gene.

Having children

If both healthy parents are carriers of the same altered recessive gene, then each child they have has a 25% (1 in 4) chance of inheriting the altered gene from both parents and therefore being affected by the condition. For each child, regardless of their sex, the chance 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 typical copies of the gene. These children will be unaffected by the condition in the family.

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 they will not be affected by the condition.
Parents who are closely related to each other, such as first cousins, are more likely to have children with recessive conditions as they share similar genetic information.

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

Further information regarding autosomal recessive inheritance is available at:

https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/autosomal-recessive-inheritance/

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

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

 

Telephone: 0151 802 5001 or 5008             Email: lwft.clingen@nhs.net  

 

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

Information for People with A Personal or Family History of Bowel Cancer or Bowel Polyps

Introduction

Lynch syndrome (previously known as HNPCC - hereditary nonpolyposis colorectal cancer) is an inherited condition which increases a person’s chance of developing bowel cancer. It also increases the chance of developing other types of cancer, including cancer of the womb (endometrial cancer), ovary, stomach, and pancreas.

How common is colorectal, womb and ovarian cancer in the general population?

The estimated lifetime chance of being diagnosed with bowel cancer is 1 in 15 (7%) for people  assigned male at birth, and 1 in 18 (6%) for people assigned female at birth, born after 1960 in the UK.¹

The estimated lifetime chance of being diagnosed with womb cancer is 1 in 36 (3%) for those born after 1960 in the UK.¹ The estimated lifetime risk of being diagnosed with ovarian cancer is 1 in 50 (2%) for those born after 1960 in the UK.¹

How common is Lynch Syndrome

Lynch Syndrome is rare: Approximately 1-3% of people diagnosed with bowel cancer will have Lynch Syndrome.²

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 a change (a variant) in one of 4 genes. These genes are called MLH1, MSH2, MSH6 and PMS2.

 These genes are known as mismatch repair (MMR) genes. MMR genes usually work to correct mistakes in DNA, but when there’s a change in these genes, any mistakes in the DNA aren’t corrected, which can lead to cancer developing.   

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 cancer and/or bowel polyp is likely to be due Lynch Syndrome. It is important to remember we can only perform tissue testing on certain types of bowel polyps.

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 or bowel polyp.

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.

What happens if NO abnormalities are identified?

If the IHC test is normal, it is much less likely that the bowel cancer or polyp   is 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 results can take up to three months to come back.  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 or bowel polyps. If this is not possible because the person with the bowel cancer or bowel polyps has passed away, consent can be obtained from one of the following people: ³

1. Spouse or partner (including civil or same sex partner). The Human Tissue 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:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008              Email: lwft.clingen@nhs.net

Further information

Cancer Research UK (http://www.cancerresearchuk.org/)

Macmillan (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

References

[1]Lifetime risk estimates calculated by the Statistical Information Team at Cancer Research UK. Based on Office for National Statistics (ONS) 2016-based Life expectancies and population projections. Accessed December 2017, and Smittenaar CR, Petersen KA, Stewart K, Moitt N. Cancer Incidence and Mortality Projections in the UK Until 2035. Brit J Cancer 2016.                                                                                                  [2]Cunningham JM, Kim CY, Christensen ER, Tester DJ, Parc Y, Burgart LJ, Halling KC, McDonnell SK, Schaid DJ, Walsh Vockley C, Kubly V, Nelson H, Michels VV, Thibodeau SN. The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas. Am J Hum Genet. 2001;69:780–90.                                                                                                                                                              [3]Human Tissue Act 2004, chapter 30. www.legislation.gov.uk/ukpga/2004/30/contents.

 

 

 

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 contains a disease-causing (pathogenic) alteration, it can cause people to have an increased chance of developing a genetic condition. A gene alteration is sometimes known as a gene variant.

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.

We have 23 pairs of chromosomes. The 23rd pair are called the sex chromosomes because they determine a person’s biological sex. Typically, females have two X chromosomes and males have one X and one Y chromosome. The Y chromosome is much smaller than the X chromosome and contains fewer genes.

Image source: https://www.genome.gov/genetics-glossary/

What does X-linked inheritance mean?

X-linked conditions occur when a gene alteration is located on the X chromosome. X-linked conditions follow either recessive or dominant inheritance patterns.

X-linked recessive conditions

In X-linked recessive conditions, if a female has a gene alteration on one of her two X chromosomes, she will usually not be affected, but will be a ‘carrier’ of the condition. She is not affected because she has a second working copy of the gene on her other X chromosome.

Some female carriers can develop features of the condition, however, these are usually mild.

If a male has a gene alteration on his X chromosome, then he will be affected by the condition, as he has only one X chromosome, and therefore only one copy of the gene.

X-linked dominant conditions

In X-linked dominant conditions, an alteration in just one copy of a gene on the X chromosome can cause the condition. This is because the altered gene is dominant over the other copy of the gene.

Both males and females can be affected by X-linked dominant conditions. Affected males tend to have more significant condition than affected females. X-linked dominant conditions are quite rare.

Having children

When a female with a gene alteration on her X chromosome has children, there is a 50% (1 in 2) chance that she will pass on the typical copy of the gene to them. There is also a 50% (1 in 2) chance that she will pass on the altered copy of the gene (see Diagram A).

When a male with a gene alteration on his X chromosome has children, all of his daughters will inherit the altered gene. Males do not pass on their X chromosomes to their sons. Therefore, sons of men with X-linked conditions are completely unaffected (see diagram B).

X-linked inheritance (Diagram A)

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

X-linked inheritance (Diagram B)

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

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.

 

 

 

 

 

The leaflet is detailed below, or you can download the 'ATM Gene Alteration'  in PDF

The ATM gene

ATM is a gene that we all have. Having an alteration in the ATM gene can increase the chance of breast cancer. The chance is affected by:

• Age
• Sex
• Family history
• Other factors e.g., lifestyle, hormonal history.

Chance of breast cancer

In the UK, breast cancer affects approximately 1 in 7* women and people assigned female at birth during their lifetime. Most of these people are aged over 60. It is very rare for men and people assigned male at birth to develop breast cancer.

*Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960.

If a genetic test shows that you have an ATM gene alteration your chance of developing breast cancer will be assessed. Women and people assigned female at birth may have a higher-than-average chance; this is likely to be a moderate chance but could be a high or very high chance. This can be due to the specific gene alteration, family history, and/or other factors.

More research could show that people with an ATM gene alteration have a higher-than-average chance of developing other types of cancer, but currently there is no evidence for this.

NB: Test results are reported based on current knowledge. Very occasionally, new information in the future may mean that our understanding of the significance of a specific gene variant may change.

Anyone with an ATM gene alteration can take part in research.

Cancer Risks and Management Options

How is the ATM gene alteration inherited?

We all have two copies of every gene including ATM. One copy is inherited from each of our parents. If we have children, we only pass on one copy of each of our genes in each pregnancy.

If an individual with an ATM gene alteration has children, there is a 50% (1 in 2) chance their ATM gene alteration could be passed on. There is also a 50% (1 in 2) chance their children could inherit the typical copy of the parent’s ATM gene. 

If someone with an ATM gene alteration has a partner who also carries an ATM gene alteration, then there is a 25% (1 in 4) chance that both parents could each pass on an ATM gene alteration to a child. This leads to a rare condition known as ataxia telangiectasia (AT). This condition causes enlarged blood vessels under the skin, uncoordinated movements, and other neurological symptoms. However, the chance of someone in the general population carrying an ATM alteration is low.

What can I do to help improve my health?

We encourage people to not smoke, to be a healthy weight, to eat less red and processed meat, to not drink too much alcohol and to exercise regularly. Doing these things can all help to reduce the chance of developing many types of cancer.

You should also report any changes in your breasts to your GP. If you have a personal or family history of breast cancer you should discuss this with your GP before taking hormone replacement therapy.

Where can I get further information?

The AT (ataxia telangiectasia) Society is a registered charity that support people who have two ATM gene alterations resulting in AT. Their website provides information and resources for people with this condition. Within the genetic aspects of AT section on their website, you can also find information about being a carrier of one ATM gene alteration.

Are there any research studies for ATM?

The Epidemiological Study of Familial Breast Cancer (EMBRACE) aims to identify risk factors contributing to the development of cancer in people with an inherited cancer gene alteration. If you are interested in discussing the possibility of participating in any research studies, please ask your Genetic Counsellor or Doctor.

This leaflet is for people who have appointments at

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5003 or 5008              

Email: lwft.clingen@nhs.net

 

 

 

 

The leaflet is detailed below, or you can download the 'BRCA2 Gene alteration' leaflet in PDF.

The BRCA2 gene

BRCA2 is a gene that we all have. Having an alteration in the BRCA2 gene can increase the chance of   breast, ovarian, prostate, and pancreatic cancer. The chance is affected by:

• Age
• Sex
• Family history
• Other factors e.g., lifestyle, hormonal history.

BRCA2 is also associated with a small increased chance of other cancers.

Chance of Cancer and Management Options

In the UK, breast cancer affects approximately 1 in 7* women and people assigned female at birth during their lifetime. Most of these people are aged over 60. It is very rare for men and people assigned male at birth to develop breast cancer.

* Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960

If a genetic test shows that you have BRCA2 gene alteration, you will have an increased chance of developing certain types of cancer. The chances for each type of cancer are shown in the table below^.   

NB: Test results are reported based on current knowledge. Very occasionally, new information in the future may mean that our understanding of the significance of a specific gene variant may change.

Anyone with a BRCA2 gene alteration can take part in research.

How is the BRCA2 gene alteration inherited?

We all have two copies of every gene including BRCA2. One copy is inherited from each of our parents. If we have children, we only pass on one copy of each of our genes in each pregnancy.

If an individual with an BRCA2 gene alteration has children, there is a 50% (1 in 2) chance their BRCA2 gene alteration could be passed on. There is also a 50% (1 in 2) chance their children could inherit the typical copy of the parent’s BRCA2 gene. 

What can I do to help improve my health?

We encourage people to not smoke, to be a healthy weight, to eat less red and processed meat, to not drink too much alcohol and to exercise regularly. Doing these things can all help to reduce the chance of developing many types of cancer.

You should also report any changes in your breasts to your GP. If you have a personal or family history of breast cancer you should discuss this with your GP before taking hormone replacement therapy.

Are there any research studies for BRCA2?

 The Epidemiological Study of Familial Breast Cancer (EMBRACE) aims to identify risk factors contributing to the development of cancer in people with an inherited cancer gene alteration. If you are interested in discussing the possibility of participating in any research studies, please ask your Genetic Counsellor or Doctor.

This leaflet is for people who have appointments at

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5003 or 5008             

Email: lwft.clingen@nhs.net

 

 

 

 

 

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

Cancer is common in the general population in the UK, with 1 in 2* people being diagnosed with a cancer during their lifetime. Most cancers are due to chance and/or environmental factors. For example, we know that the chance of developing cancer increases as we get older, and that lifestyle factors such as smoking, drinking alcohol and being overweight increase the chance of developing many cancers. Some cancers occur due to inherited genetic factors. We are more suspicious of there being an inherited cause for the cancers in a family if the same or related cancers occur across multiple generations, are diagnosed at younger than expected ages, with more people developing cancer than we would expect by chance.

*Cancer research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960

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.

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

Image Source: https://cpmc.coriell.org

We have 23 pairs of chromosomes and one of each pair is inherited from each parent. Chromosomes contain an estimated 20-30,000 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. 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 variant, a spelling mistake or a mutation.

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

What is Lynch syndrome?

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

There are currently 4 mismatch repair genes that we know of that act like a quality control system; MLH1, MSH2, MSH6 and PMS2. They help protect us from developing cancer by detecting and correcting errors that can occur in DNA when cells copy themselves (DNA replication errors). Having a pathogenic variant in one of these genes means that the quality control system is less effective and the person has Lynch syndrome, and so is more likely to develop certain types of cancer. Having Lynch syndrome does not mean a person will definitely go on to develop cancer.

Having Lynch syndrome causes a high chance of developing bowel cancer. People with Lynch syndrome who were assigned female at birth also have a high chance of endometrial (womb) cancer and often a high chance of ovarian cancer, depending on the particular gene in which the pathogenic variant is found. Additional screening and/or risk-reducing measures may be advised depending on individual risks. There may also be a slightly increased chance of developing other cancers including kidney (renal) cancer and pancreatic cancer but not enough to warrant routine screening unless there is a family history. It is important to have a low threshold for seeking medical help for any concerning or persistent symptoms.

What are the main cancer risks associated with having Lynch syndrome?

What can be done to help manage these increased risks? 

Management option	MLH1		MSH2			MSH6	PMS2
Colonoscopy screening	Every 2 years aged 25-75 Review at 75		Every 2 years aged 25-75 Review at 75			Every 2 years aged 35-75 Review at 75	Every 2 years aged 35-75 Review at 75
Gastric screening	H Pylori one off screening from 25		H Pylori one off screening from 25			H Pylori one off screening from 25	H Pylori one off screening from 25
Aspirin chemoprevention	Discuss with GP the pros and cons of taking aspirin, further details below		Discuss with GP the pros and cons of taking aspirin, further details below			Discuss with GP the pros and cons of taking aspirin, further details below	Discuss with GP the pros and cons of taking aspirin, further details below
Risk-reducing gynaecological surgery		Surgery to remove the womb, ovaries and fallopian tubes (hysterectomy and bilateral salpingo-oophorectomy) No earlier than 35-40 and once childbearing complete   HRT should be offered until 51 in women who have not had ER +ve breast cancer Everyone with a cervix should attend for their regular cervical smears		Surgery to remove the womb, ovaries and fallopian tubes (hysterectomy and bilateral salpingo-oophorectomy) No earlier than 35-40 and once childbearing complete HRT should be offered until 51 in women who have not had ER +ve breast cancer Everyone with a cervix should attend for their regular cervical smears	Surgery to remove the womb, ovaries and fallopian tubes (hysterectomy and bilateral salpingo-oophorectomy) No earlier than 35-40 and once childbearing complete HRT should be offered until 51 in women who have not had ER +ve breast cancer Everyone with a cervix should attend for their regular cervical smears			Surgery to remove the womb (hysterectomy) No earlier than 45 and once childbearing complete                                                                Everyone with a cervix should attend for their regular cervical smears

What does a colonoscopy involve?

A colonoscopy is an internal examination of the large bowel. The purpose of a colonoscopy is to look for bowel 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, some polyps do have the potential to turn cancerous if left to grow over time, as illustrated:

Image source: NHS National Genetics and Genomics Education Centre

By removing any polyps during a colonoscopy, this reduces the chance of them turning cancerous.

What does gastric screening involve?

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 with Lynch syndrome. H.pylori can be detected by a breath test, blood test or stool sample and if found, eradicated with a course of antibiotics.

Why should I discuss aspirin use with my GP?

Aspirin taken daily for 2 years or more could reduce the risk of colorectal (bowel) cancer in people with Lynch syndrome, says National Institute for Clinical Excellence, NICE guidance 151.  Aspirin is not licensed for this purpose so if it is prescribed for cancer risk reduction this is called an ‘off-label’ use of aspirin. 

The best dose of aspirin is not yet clear, but the UK Cancer Genetics Group recommend those between 25 and 65 years consider taking 150mg if 70kg or under and 300mg for people who weigh more than 70kg. These recommendations are likely to be updated over the coming years as more evidence becomes available. 

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 consideration of aspirin usage to anyone without Lynch syndrome.

Can I have screening for ovarian and endometrial cancer rather than surgery?

Screening for ovarian cancer and endometrial cancer is not proven to be effective in detecting these cancers at an early enough stage in order for them to be treated effectively. Therefore, it is advised that people with Lynch syndrome who have a womb (and/or ovaries) consider risk-reducing gynaecological surgery as detailed above.

What else can I do to help protect my health?

We encourage people to not smoke, to maintain a healthy BMI, to limit their consumption of red and processed meat, and to exercise regularly. Doing these things can all help to reduce the chance of developing many types of cancer.

How is Lynch syndrome passed down (inherited) through families?

Lynch syndrome is inherited in an autosomal dominant inheritance pattern. We have two copies of each of the mismatch repair genes and if one copy has a variant then this means the person has less protection against developing certain types of cancer and they have Lynch syndrome. Each time someone with Lynch syndrome has a child, there is a 50% chance of passing on the working copy of the gene and a 50% chance of instead passing on the gene variant causing Lynch syndrome. Someone with Lynch syndrome has usually inherited this from one of their parents.

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

What is predictive testing?

Predictive testing is offered to family members who may have inherited a specific gene variant that has been identified in the family. 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 agreed 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.

NB: Test results are reported based on current knowledge. Very occasionally, new information in the future may mean that our understanding of the significance of a specific gene variant may change.

What are the issues to think about when deciding whether or not to have a gene test?

A predictive genetic test tells us whether or not you have inherited the specific gene variant known to cause Lynch syndrome in your family. It can be difficult to make a decision about whether or not to have a predictive test and there are reasons for and against it. 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 Lynch syndrome?

For some people, knowing that they have inherited the gene variant causing Lynch syndrome is preferable to living with the uncertainty of not knowing. 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 Lynch syndrome.

How do you think you would cope if the test were to show that you have not inherited the familial gene variant?

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

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

What are the possible implications for children?

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 the gene variant 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. Predictive testing for Lynch syndrome is offered in adulthood as there is not thought to be any increased risk of cancers in childhood.

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 Lynch syndrome 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 had 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 scientists in the genetic laboratory would test the sample to find out whether or not you have inherited the gene variant 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 LIVERPOOL CENTRE FOR GENOMIC MEDICINE 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 on insurance and genetics:

The Association of British Insurers Genetics Frequently Asked Questions  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 Lynch syndrome, but for couples who wish to consider this, some of the choices can include:

• Preimplantation genetic testing (PGT-M)

Pre-implantation genetic testing (PGT-M) is a special type of in vitro fertilisation (IVF) which is available to couples who have an increased chance of having a child with a specific genetic condition. The aim is to avoid passing on the genetic condition to the child.

More information can be obtained at https://www.guysandstthomas.nhs.uk/our-services/pgd/about-us/welcome.aspx

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

Our experience is that very few people who have Lynch syndrome choose any of the above options.

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:

Liverpool Centre for Genomic Medicine                                                                                              Liverpool Women’s Hospital NHS Foundation Trust                                                                                Crown Street                                                                                                                                    Liverpool                                                                                                                                 

L8 7SS                                                                                                                                            Telephone: 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The leaflet is detailed below, or you can download the 'Genomic Testing – Cancer Panel' leaflet 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 related 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.

*Cancer research UK (2015) Estimated Lifetime Risk of being diagnosed, people born after 1960

What are genes and chromosomes?

Humans are made up of trillions of cells.  At the centre of almost all of our 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 metres 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 panel testing?

Traditionally, genetic tests were targeted at just one gene. This meant that the health professional providing your care needed to have a strong idea of what was causing the cancers in a family in order to choose the correct test. This is not always possible with cancers that may not fit an obvious pattern or when the cancers could be caused by changes in one of a large number of genes. In many instances that meant multiple tests of several genes over a period of time, and more laboratory time and effort was needed to obtain a result. With new technologies it is possible to examine many different genes at the same time. 

Targeted panel testing is a technique in which a number of specific genes that are linked to a particular cancer or related cancers are examined at the same time.

If I undergo panel testing, what will my results show?

Your results will show one of 3 things:

1. A gene alteration is identified in your sample that is known to be disease causing (pathogenic). This is highly likely to be the cause of the cancers in your family. Usually we know this because it has been found in many others with the same cancer. This gene alteration may also confer other increased risks and your genetic counsellor or doctor will discuss this with you when they provide you with your results. 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.
2. No pathogenic gene alteration is identified. This does not necessarily mean there is not an inherited genetic explanation for the cancers in your family but it may be that within the confines of current technology we have been unable to detect a gene alteration. Alternatively 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.
3. A gene alteration has been found but we are not sure if it is significant or not. This is also sometimes called a variant of unknown significance (VUS) or an unclassified variant (UV). Finding this may mean we have to undertake more testing in the family or that we may need to look at the VUS 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.*

It is very important to remember that the genes we test can also be associated with a whole range of other problems that can impact your health and may mean you need additional screening or other tests.

In general, your genetic counsellor or doctor may think it is helpful to tell you about anything that is found that is actionable. This means that there is known to be a risk to your health and your genetic counsellor or doctor can advise you about screening or treatment that could be helpful to prevent or treat the condition.

There is also a possibility that you could be found to have a gene alteration that does not affect your own health but may result in an increased risk of having an affected child. For example, some genetic conditions (called autosomal recessive conditions) arise when a child inherits a gene alteration from both parents and has no normal copy of that gene. Healthy carrier parents have one normal and one faulty copy of the gene and do not usually have any problems associated with the condition. A genetic test may indicate you are a healthy carrier of a condition, and if so you will be given information about what this means for your family.

How are gene alterations passed down (inherited) through families?

Gene alterations can be passed down by several different patterns of inheritance. The specific inheritance pattern helps us to inform the chance of other family members being found to have the same gene alteration and therefore their chance of developing cancer(s).

Your genetic counsellor or doctor will provide you with information and additional leaflets about the inheritance patterns relevant to the genes in the panel test that is being offered to you.

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 and so sharing genetic information in a family is really important. It can provide family members with a real opportunity to protect their health, for example by enrolling in screening programmes or even surgical options.

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 ‘Dear Family Member 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.

Should I tell my children?

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 provide your consent and we will arrange for you to have a blood sample taken.

The laboratory team will then extract the DNA from your blood sample. They will search through the DNA of the specific set of genes on the panel to see if the code in any of these genes differs from that of a normal gene. Often, genes are large and can take a long time to be looked through. The time that we would expect results to be ready in differs between panel tests and your genetic counsellor or doctor will advise you on this.

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.

IF, FOR SOME REASON YOU HAVE NOT RECIEVED YOUR RESULTS WITHIN THE EXPECTED TIMEFRAME GIVEN TO YOU, PLEASE CALL THE LIVERPOOL CENTRE FOR GENOMIC MEDICINE 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. These numbers can be found on any letter sent from the Genetics Department.

What happens if I choose not to go ahead with having a test?

We will not be able to offer predictive testing to your relatives but we may be able to make screening recommendations for your relatives based on the family history.

Attending your appointment with Genomic Medicine 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.

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 Questions 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

 

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

 

 

 

 

 

 

The leaflet is detailed below, or you can download the 'Genomic Testing - Non-Cancer Panel' leaflet in PDF.

Introduction

For many people with a genetic condition finding out the cause of the condition can be important.  Understanding the genetic basis of the condition might help health professionals to give you information about the progress of the condition, possible preventive actions or treatment. Individuals with a genetic condition may just find it helpful to know why their signs and symptoms occur.  

What are genes and chromosomes?

Humans are made up of trillions of cells.  At the centre of almost all of our 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 metres 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 panel testing?

Traditionally genetic tests were targeted at just one gene. This meant that the health professional providing your care needed to have a strong idea of what was causing the condition in order to choose the correct test. This is not always possible with conditions that may not fit an obvious pattern or when the condition could be caused by changes in one of a large number of genes. In many instances that meant multiple tests of several genes over a period of time, and more laboratory time and effort was needed to obtain a result. With new technologies it is possible to examine many different genes at the same time. 

Targeted panel testing is a technique in which a number of specific genes that are linked to a particular genetic condition are examined at the same time. Examples of conditions for which targeted gene panels have been developed are hearing impairment, epilepsy and eye disorders, which may be caused by alterations in one of many separate genes. With this test, even though we might be looking at a number of different genes, the analysis is targeted on the specific condition present in the family.

It is important to remember that the genes we test can also be associated with a range of other problems that can impact your health and may mean you need additional screening or other tests.

If I undergo panel testing, what will my results show?

Your results will show one of 3 things:

1. A gene alteration is identified in your sample that is known to be disease causing (pathogenic). This is highly likely to be the cause of your condition or contributes to it in some way. Usually we know this because it has been found in many others with the same condition. 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.
2. No pathogenic gene alteration is identified. This does not necessarily mean there is not an inherited genetic explanation for your condition but it may be that, within the confines of current technology, we have been unable to detect a gene alteration. Alternatively, 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.
3. A gene alteration has been found but we are not sure if it is significant or not. This is also sometimes called a variant of unknown significance (VUS) or an unclassified variant (UV). Finding this may mean we have to undertake more testing in the family or that we may need to look at the VUS 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.*

It is very important to remember that the genes we test can also be associated with a whole range of other problems that can impact your health and may mean you need additional screening or other tests.

In general, your genetic counsellor or doctor may think it is helpful to tell you about anything that is found that is actionable. This means that there is known to be a risk to your health and your genetic counsellor or doctor can advise you about screening or treatment that could be helpful to prevent or treat the condition.

There is also a possibility that you could be found to have a gene alteration that does not affect your own health but may result in an increased risk of having an affected child. For example, some genetic conditions (called autosomal recessive conditions) arise when a child inherits a gene alteration from both parents and has no normal copy of that gene. Healthy carrier parents have one normal and one faulty copy of the gene and do not usually have any problems associated with the condition. A genetic test may indicate you are a healthy carrier of a condition, and if so you will be given information about what this means for your family.

How are gene alterations passed down (inherited) through families?

Gene alterations can be passed down by several different patterns of inheritance. The specific inheritance pattern helps us to inform the chance of other family members being found to have the same gene alteration and therefore their chance of developing a particular condition.

Your genetic counsellor or doctor will provide you with information and additional leaflets about the inheritance patterns relevant to the genes in the panel test that is being offered to you.

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 family history 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 will also 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 and so sharing genetic information in a family is really important. It can provide family members with a real opportunity to protect their health, for example, by enrolling in screening programmes or even surgical options.

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 a condition 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 ‘Dear Family Member 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.

Should I tell my children?

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 provide your consent and we will arrange for you to have a blood sample taken.

The laboratory team will then extract the DNA from your blood sample. They will search through the DNA of the specific set of genes on the panel to see if the code in any of these genes differs from that of a normal gene. Often, genes are large and can take a long time to be looked through. The time that we would expect results to be ready differs between panel tests and your genetic counsellor or doctor will advise you on this.

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.

IF, FOR SOME REASON, YOU HAVE NOT RECIEVED YOUR RESULTS WITHIN THE EXPECTED TIMEFRAME GIVEN TO YOU PLEASE CALL THE LIVERPOOL CENTRE FOR GENOMIC MEDICINE 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. These numbers can be found on any letter sent from the Genetics Department.

What happens if I choose not to go ahead with having a test?

We will not be able to offer predictive testing to your relatives but we may be able to make screening recommendations for your relatives based on the family history.

Attending your appointment with Genomic Medicine 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.

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 Questions  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

 

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

 

This leaflet is detailed below The leaflet is detailed below, or you can download the 'Liverpool Centre for Genomic Medicine (LCGM) A guide to your referral'  leaflet in PDF.

This leaflet provides important information to help people who are referred to us. It aims to answer some of the common questions we are asked.

Why have I been referred to Liverpool Centre for Genomic Medicine?

Genomic medicine is the medical specialty for individuals or families with, or at risk of, conditions which may have a genetic basis. Genetic disorders can affect any body system and any age group.

Before your appointment

We offer different types of appointments in different hospitals in the region. You may see a Doctor or Genetic Counsellor in clinic, and we also offer telephone and video appointments.

Therefore, we ask patients to carefully note the time, date and location of their appointment to avoid missing it.

We will always try and provide you an appointment that is closest to you but this is not always possible due to waiting times or suitability e.g. some of our clinics are only suitable for children.

Please note: our clinic rooms at the Liverpool Women’s Hospital are in the antenatal clinic. If you feel it would be difficult for you to be seen in an antenatal department please ring and we may be able to offer you an appointment at one of our other clinic sites.

Family History Collection Team (FHCT)

The FHCT may contact you before your appointment.  Their job is to gather information in preparation for your appointment to make the appointment as useful as possible.  They may take details of people in your family who have had genetic testing, draw a family tree or make a note of the growth and development of your child.  The FHCT are non-clinical members of staff and will not be able to answer any questions in relation to the reason you have been referred to LCGM. However, they can note down any specific questions you would like answering in your appointment. 

What if I have a disability such as a visual or hearing impairment or I need support to get to or at an appointment or I need a translator?

Please ring or email us to let us know if you require additional support in your appointment and we will do our best to accommodate your needs.  See contact details below.

Parking

Parking availability and cost of parking varies. Please check where your appointment is and look at that hospital’s website for parking details.

At my appointment

You will be seen by a member of the genomic medicine team. This may be a Doctor who specialises in genetics or a Genetic Counsellor.

Most genetic appointments are 45 to 60 minutes long, so you should not feel rushed. We are happy for friends or family to attend with you to provide support.

What happens in your appointment will vary depending on the reason for your referral but may include:

• A detailed discussion of the reason that has brought you to the clinic
• The drawing of a family tree (if not drawn up beforehand) and medical details of relatives may be asked about (such as the cause and age of their death). It is useful to have found out these details before you come to the clinic or bring a relative who will know. ·
• A medical examination may be carried out if appropriate.

The doctor/genetic counsellor will explain their assessment to you and discuss your options and choices. You will be encouraged to ask questions and to make your own decisions.

In some situations, tests (such as blood tests) may be offered. Some tests are available on the day of your appointment, but often you will be asked to take some time to make a decision and come back. The results from genetic testing often take several weeks to several months, so, even if you have a blood sample taken on the day of your appointment, you will not receive any results the same day.

At the end of the appointment a plan will be made. This may include information gathering, special tests and/or another appointment

My child has been referred to the LCGM, should I bring them to the appointment?

Your child will need to come to the appointment if an examination is required. However, we can offer you another appointment without your child if you have any questions, you would rather not ask in front of them. We always encourage children to be involved in their appointment and we will not offer genetic testing to a child without including them in any discussions if possible. We will always try and tailor the appointment to be age appropriate.

After your appointment

We will send you a summary letter. If anything in this is unclear, please do not hesitate to contact the department with any queries.

Please note: there is an option to have your letter and any other correspondence sent via email. Do not hesitate to ask your clinician for this option if you have not been asked.

We will write to your GP and the referring doctor unless you specifically ask us not to do so. If genetic tests have been done, we will arrange to give you the results once they are available. Arrangements may be suggested for other family members to be referred.

Where else can I get information before my appointment?

Liverpool Women’s Hospital Website: www.liverpoolwomens.nhs.uk

NHS Choices: https://www.nhs.uk

Genetic Alliance: https://geneticalliance.org.uk/

Cancer Research UK: Cancer Research UK

Feedback welcome

We strive to continually improve the service we deliver in the best way we can and your feedback is very important to us. You will receive a ‘friends and family’ text after your appointment which will provide you with the opportunity to feedback your experience. Comments, suggestions and complaints can also be made through PALS. Call 0151 702 4353 or email PALS@lwh.nhs.uk

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

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown St. Liverpool, Merseyside L8 7SS

Telephone 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

 

 

 

 

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

Introduction

The doctor looking after you / your child has decided to request a test called a 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 will 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, unusual fingers or toes and many others.

What is a microarray?

A microarray test looks at the chromosomes in fine detail and can pick up tiny pieces of missing or extra chromosome that may cause a range of developmental and health issues. Missing pieces of chromosome are called deletions, and extra pieces are called duplications.

What happens now?

A blood sample will be needed from you or your child and sent to our laboratory for a microarray test. Results may take approximately 12 weeks and the doctor will contact you once the results are known.

If the laboratory has a sample of DNA stored from a previous genetic test, it may be possible to test this DNA sample although a new blood sample may be required in certain circumstances.

Results

There are four possible outcomes from the microarray:

1. The chromosomes may appear entirely normal. However, 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.
2. The test may reveal a change which is highly likely to account for the problems that you or your child has, and you would be offered an appointment to discuss this further.
3. We may 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 the issue. In this case, further investigation may be needed such as getting DNA samples from parents. However, some changes will remain uncertain.
4. There is also a very small chance that we could detect something unrelated to you / your child’s current problems but may have implications for you, your child or your family’s future health e.g. early onset cancer or heart disease. You would be offered an appointment to discuss this further.

If you need more advice about the microarray test, please contact the doctor who has offered you the test.