Marfan Syndrome and Genetics

Season: 2001

Submitted By: Dr. Francois Bernier (Marfan Symposium 2001)

Genetics is a rapidly expanding field. In the last 20 years research publications about Marfan Syndrome have increased dramatically with the emphasis now being placed on genetics and more specifically the fibrillin gene.

In our body we have over 30,000 genes with each gene having one or more functions. Most genes make proteins, one of which is fibrillin. Marfan Syndrome is caused by an abnormality in fibrillin.

Marfan Syndrome is an autosomal dominant condition. This means that both sexes can be affected equally and that one abnormal copy of a gene is enough to result in the condition. In a "typical" Marfan Syndrome family, an affected individual has a 50% chance of passing on the condition with each pregnancy. Normally, unaffected individuals do not have a risk of having an affected child.

25% of Marfan patients have no family history. This is because their condition is caused by a new change, called a new mutation. An affected individual will now have a 50% chance of passing it on with each pregnancy. Unaffected parents have only about a 5% chance of having 2 children with Marfan Syndrome. Why does this happen? New mutations are common because each time a cell divides, it copies over 3 billion letters and the fibrillin gene is a large gene. Each of us passes on at least several new mutations each time we have a child. Most of these will have no consequence, some will be beneficial, and some will be in important genes.

The gene for Marfan Syndrome has been found on chromosome 15. So if we know where it is why do we not do DNA testing? First of all, the gene is large with a code of over 100,000 letters long and at this time is too labor intensive and expensive. As well, over 150 different genetic changes have been identified with most families having their own unique change. Lastly, not all mutations in the fibrillin gene result in Marfan Syndrome.

Available genetic testing includes linkage analysis and direct gene testing. Linkage analysis requires several affected and unaffected family members. It does not identify the genetic change, but "tracks" the affected chromosome. Direct gene testing looks for the genetic change. It is expensive and only about 70% of the patients with Marfan Syndrome will have a mutation identified. It is possible to miss the mutation. Linkage analysis would be the preferred method to determine if an affected individual in a known Marfan family has the disorder as well as to offer prenatal testing for large families. Direct gene testing could be done for prenatal testing in small families or families with only a single affected individual. The diagnosis of Marfan Syndrome still remains a clinical one using the defined criteria.

As more advances are made in the field of genetics, new options may become available, some as soon as 5 years from now. We do not know at this time whether they will be beneficial in Marfan Syndrome.