The Genetics

Genetic disorders occur as the result of defective genes that are passed on to the baby from the mother, the father, or both. Marfan Syndrome is an autosomal dominant disease. Autosomal means the mutation is in a gene located on one of the 22 pairs of autosomes, which are the numbered chromosomes that are the same in all males and females, since the 23rd pair are the sex chromosomes. Dominant refers to a gene that is always expressed, even if only one copy is present. When a parent with Marfan Syndrome passes on a mutated copy of the gene to his/her child, the child will inherit the disorder. However, a parent with the syndrome is also capable of passing on a normal (unchanged) copy of the gene. If a child inherits this normal gene, then he/she will not have the disorder.

Below is an example of a punnett square with one homozygous dominant parent with Marfan Syndrome (RR), and one parent who does not have Marfan Syndrome at all (rr). Since every possible outcome is homozygous (Rr), their child will definitely inherit the disorder, because the syndrome is dominant and therefore carried by the capital R. This means that one capital R is all that is needed for the syndrome to be expressed.

Below is different example of a punnett square with one heterozygous parent (Rr) with Marfan Syndrome, and one parent who does not have Marfan Syndrome at all (rr). Their child will have the disorder if they happen to be Rr, but will not have the disorder if they turn out to be rr, so it is a 50-50 chance.

If both parents have the disorder, then their children are guaranteed to have it as well. However, it is also possible for an individual to develop Marfan Syndrome even if neither parents have it at all. This is caused by a spontaneous gene mutation that happens in either the egg or sperm at the time of conception. Unaffected parents only have about a 1 in 10,000 chance of having a child with the syndrome.

As described in this article, scientists were able to discover the gene that caused Marfan Syndrome in 1991. Further studies allowed the exact position to be pinpointed. The FBN1 gene is located on the long arm (q) of chromosome 15 at position 21.1, from base pair 48,408,305 to base pair 48,645,787. 

The FBN1 gene (Source)

This gene encodes a large protein called fibrillin-1, which is a major building block of microfibrils. Microfibrils are structural components of the supporting matrices of the tissue of the eyes, aorta, lung airways, and the dura of the spinal column. Mutations in FBN1 reduce the amount of fibrillin-1 produced by the cell, alter the structure or stability of fibrillin-1, and/or impair the transport of fibrillin-1 out of the cell. This resuts in a severe reduction in the amount of fibrillin-1 available to form microfibrils. Without enough microfibrils, the overgrowth and instability of connective tissues in many parts of the body cause the signs and symptoms of Marfan syndrome to occur.