Genetic counselling for the Ehlers-Danlos syndromes
Marion McAllister, Genetic Counsellor and MRC Research Fellow, University of Manchester & Judy Tocher, Genetic Counsellor, EDS National Diagnostic Service, Sheffield Children's Hospital
Please note: The following text cannot and should not replace advice from the patient's healthcare professional(s). Any person who experiences symptoms or feels that something may be wrong should seek individual, professional help for evaluation and/or treatment. This information is for guidance only and is not intended to provide individual medical advice.
Much of this article has been modified from leaﬂets produced by Guy’s and St Thomas’ Hospital, London, and the London IDEAS Genetics Knowledge Park.
The Ehlers-Danlos syndromes are genetic conditions. This means that if someone has a diagnosis of EDS, other members of the family may be at risk of having the condition or passing it on to their children. Clinical genetics is the NHS service that could tell you more about this. Diagnosis of EDS can be made by any doctor, such as a dermatologist, rheumatologist or clinical geneticist. You may benefit from being seen by your local clinical genetics service, even if another branch of medicine has made the diagnosis.
Clinical genetics departments are organised in 25 regional centres. Some but not all centres have outreach clinics in local areas. Referral is usually either through your GP or a hospital doctor. The health professionals that work in a clinical genetics service include specialist doctors, called clinical geneticists, and genetic counsellors.
What is a genetic counsellor?
Genetic counsellors can give people information about genetic conditions and how they are inherited, and they work very closely with clinical geneticists. Clinical geneticists are qualified to diagnose genetic conditions. The role of a genetic counsellor is to help a family to understand better the implications of a diagnosis of a genetic condition in a family. This includes helping the family to understand who else in the family might be at risk and how the condition is inherited. They may also help the family to make decisions about management of the condition. For certain forms of EDS, there are tests available during pregnancy, and some people may wish to discuss these with their genetic counsellor. By exploring available options, families can make their own informed decisions about pregnancy and other matters.
What are the possible benefits of genetic counselling?
Families who have had genetic counselling report that it can help them to:
- Gain a better understanding of the condition in the family
- Make decisions about the condition in the family
- Talk about the condition to other people in the family who might be at risk
- Take action to better manage the family condition, and
- Communicate with health professionals, teachers, social workers, etc about their needs.
Different people may handle genetic information in different ways, depending on their own personal beliefs and their past experiences. Genetic counsellors can help individuals to make their own decisions in the context of their own unique medical, moral and social situation.
What happens at a Genetics Clinic appointment?
Practice may vary between genetic centres, but a genetics consultation will usually last between 30 and 45 minutes. It may involve one or more of the following:
- Discussing your particular concerns
- Discussing your medical history
- Drawing your family tree, which can give valuable information that can help make a definite diagnosis, and identify who else may be at risk in the family. It is therefore useful to find out as much as you can from your relatives prior to your appointment, and to bring this information with you when you come for your appointment.
If you have been referred because you or your child is suspected of having EDS, then your appointment will involve a physical examination. A doctor will examine your skin looking for scars, and determine how stretchy and soft your skin is. S/he will also assess your joints, and how bendy they are. The doctor may wish to take some photographs of your skin and joints, with your permission. These will form part of your medical record, and if necessary, will enable the doctor to discuss your case with colleagues.
The doctor will then assess how likely it is that EDS may be present in your family. It may not be possible to determine this for certain at your first appointment. There are many types of EDS, and sometimes further tests are required before a diagnosis can be made. So it is possible that you may need to come to the Genetics Clinic more than once.
If and when a definite diagnosis is made, the counsellor/doctor can then explain things in more detail, and try to help you understand the facts, in everyday language.
How are the Ehlers-Danlos syndromes inherited?
There are different types of EDS, but all are caused by an underlying change in a gene. Genes are the unique instructions which make each of us an individual. There are many thousands of different genes, each carrying a different instruction. If a gene is changed in some way, it can cause a genetic condition. The body is made up of millions of cells, and genes are found in every cell of the body.
There are approximately 25,000 different genes, and we have two copies of each. One copy is inherited from each parent. When we have children, we pass on one copy of each of our genes. There are different inheritance patterns for different genetic conditions, including the different types of EDS. Some types of EDS are inherited in a ‘dominant’ pattern; others are inherited in a ‘recessive’ pattern.
Genetic conditions that show dominant inheritance are caused by an alteration in one copy of a particular gene pair. The altered copy of the gene is dominant over the other, normal copy of the gene. Having a normal copy of the gene cannot prevent the disease from occurring.
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 families affected by a dominantly inherited genetic condition, it is most common to see people affected in each generation of the family tree. Even within a family, some individuals may be affected by the same dominant condition in different ways, and the severity can be variable. In some dominant conditions, it is possible for someone to inherit an altered gene without showing any or all symptoms of the condition. This person could then go on to have an affected child, which may make the disease appear to have skipped a generation. In reality, the altered gene did not skip a generation at all, but the symptoms of the disease were mild or went undetected so that it may have appeared to miss a generation.
In some families, an isolated case of a dominant disorder may be the result of a new gene change (a change which arises for the first time) in either the egg or the sperm that went to make that child. In these cases, that child could go on to have affected children themselves in the future. Classical, vascular and arthrochalasia are types of EDS that are known to be dominantly inherited. The exact cause of hypermobile EDS is unknown but in most families appears to be inherited in a dominant pattern.
Genetic conditions that show recessive inheritance are caused by gene alterations in BOTH copies of a particular gene pair. As there is no working copy of the gene, then the body is missing a particular instruction and that person will be affected with the genetic condition.
When having children, each parent passes on one copy of each gene pair in the egg or sperm. This happens completely randomly; we have no control over which genes we pass on. If both parents carry 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 with the condition.
- 50% (1 in 2) chance of inheriting one copy of the altered gene and one normal copy. If this happens, they are healthy carriers
- 25% (1 in 4) chance of inheriting two normal copies of the gene, therefore having no related problems.
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 depending on which copy of the gene pair the carrier parent passes on.
Parents who are closely related to each other, such as first cousins, are more likely to have children with recessive conditions. This is because they have a higher chance of both being carriers of the same genetic condition.
Types of EDS that are recessively inherited include kyphoscoliotic and dermatosparaxis.
For some people it may be possible to do a blood test to find the specific gene change in the family. This type of blood test is called a ‘genetic test’. It may take many months for any results of genetic testing to become available, and genetic testing is not always possible. A genetic test can confirm a diagnosis made on the basis of a doctor’s examination. A genetic test can sometimes be used to predict whether a person will go on to develop EDS, or it can be used in pregnancy to determine whether or not the baby will be affected. As these tests do have important implications for other people in the family, further genetic counselling sessions may be appropriate. The purpose of further appointments is to give you time to consider these issues and to discuss them in greater detail, and to help you to make decisions about whether or not a genetic test is right for you.
The EDS National Diagnostic Service
Sometimes, it is not straightforward to make a diagnosis of EDS, and a national specialist EDS service has been set up to help in situations where a diagnosis is suspected, but hard to make. Referrals can be made by NHS hospital consultants for patients in whom the diagnosis of EDS is suspected but not confirmed for one of the following reasons:
- Signs and symptoms of the condition are not typical
- Genetic testing does not confirm the diagnosis suspected
- The signs and symptoms fit more than one type of EDS
- There are other signs and symptoms that are not typical of EDS
Referrals are also accepted where the patient or clinician requests a second opinion. Referrals cannot be accepted from your GP.
Ehlers-Danlos Syndrome National Diagnostic Service
Sheffield Clinical Genetics Department
Sheffield Children’s Hospital
Sheffield S10 2TH
Tel: 0114 271 7764
Ehlers-Danlos Syndrome National Diagnostic Service
Northwick Park & St Mark’s Hospitals
Middlesex HA1 3UJ
Tel: 020 8869 3166