Antoine Marfan and his syndrome: one hundred years later

In 1896, in the Bulletin of the Medical Society of Paris, Antoine Marfan described a five-year-old girl with arachnodactyly. It took almost 50 years to fully elucidate this syndrome including aneurysm of the ascending aorta. It is critical to make an early diagnosis of Marfan aneurysm because there is a high frequency of dissection and rupture once the aortic diameter reaches 6 cm. Before the availability of the Bentall composite graft procedure in 1968, the operative results were very poor. The Bentall operation now carries a 30-day mortality rate of less than 5% at major cardiac surgical centers. Two hundred and thirty-one Marfan patients underwent aortic root replacement at The Johns Hopkins Hospital between September 1976 and December 1997. The 30-day mortality for 198 patients undergoing elective aortic root replacement was 0%. Two of 33 patients undergoing urgent surgery died in the first 30 days after surgery; both of these patients arrived in the operating room with ruptured aortas. The actuarial survival for the 231 patients undergoing aortic root replacement was 88% at five years, 81% at ten years, and 75% at 20 years. Clearly, the outlook for Marfan patients undergoing elective aortic root replacement has been excellent. Accompanying the steadily improving surgical results have been spectacular developments in understanding the genetic role in Marfan families. Since 1991, over 150 mutations have been discovered in the gene that is critical in the production of the structural protein fibrillin. The identification of mutations in the fibrillin gene has enabled the diagnosis of Marfan disease in some patients before they become symptomatic; prenatal diagnosis has been achieved in some patients. The ultimate hope for Marfan families is to eliminate the disease by genetic manipulation; however, this may be years away.