Marfan syndrome is an autosomal dominant genetic disorder of the connective tissue characterized by disproportionately long limbs, long thin fingers, a typically tall stature, and a predisposition to cardiovascular abnormalities, specifically those affecting the heart valves and aorta. The disorder may also affect numerous other structures and organs — including the lungs, eyes, dural sac surrounding the spinal cord, and hard palate. It is named after Antoine Marfan, the French pediatrician who first described it in 1899.
Marfan syndrome affects males and females equally, and the mutation shows no geographical bias. Estimates indicate that approximately 60 000 (1 in 5000, or 0.02% of the population) to 200 000 Americans have Marfan syndrome. Each parent with the condition has a 50% chance of passing it on to a child due to its autosomal dominant nature. Most individuals with Marfan syndrome have another affected family member, but approximately 15-30% of all cases are due to de novo genetic mutations — such spontaneous mutations occur in about 1 in 20 000 births. Marfan syndrome is also an example of dominant negative mutation and haploinsufficiency (Haploinsufficiency occurs when a diploid organism only has a single functional copy of a gene (with the other copy inactivated by mutation) and the single functional copy of the gene does not produce enough of a gene product (typically a protein) to bring about a wild-type condition, leading to an abnormal or diseased state. Haploinsufficiency is therefore an example of incomplete or partial dominance, as a heterozygote (with one mutant and one normal allele) displays a phenotypic effect.
A Haploinsufficient gene is therefore described as needing both alleles to be functional in order to express the wild type. A mutation is not haploinsufficient, but dominant loss of function mutations are the result of mutations in haploinsufficient genes.).
Marfan syndrome is caused by mutations in the FBN1...