Scientists at the Johns Hopkins University and the Shriners Hospital in Portland, Ore., have identified the gene responsible for Marfan syndrome, a discovery that has spawned a test capable of diagnosing the disorder before deadly symptoms appear.
A cure might still be many years off, but the discovery could save lives, since it offers patients the chance of diagnosis early in life and treatment -- such as drugs or surgery -- to prevent or delay fatal complications.
Within a year, scientists predict, a prospective parent whose family has been plagued by Marfan will be able to get a prenatal diagnosis.
"This is a very personal issue, not something we would inflict an opinion on," Dr. Harry C. Dietz of Hopkins, the principal author of an article in today's issue of Nature, said yesterday at a news briefing. "But we can't deprive families of this information."
Marfan, which strikes one in 10,000 people, is a disorder of the connective tissue that holds together skin, muscles and organs. Its symptoms include tall stature; elongated arms, fingers and toes; nearsightedness; dislocation of eye lenses; overly flexible joints; and a stretched, fragile aorta, the heart's main blood vessel.
At least two star athletes, Olympic volleyball player Flo Hyman and University of Maryland basketball player Chris Patton, have died during competition when their Marfan-weakened coronary arteries burst.
Those with the disease may have some or all of the symptoms, which can range from severe to mild. Marfan's variability often makes it difficult to diagnose, a problem that underscores the excitement of some sufferers, parents and scientists over yesterday's announcement.
"It would have made a big difference for my family and myself to have a diagnosis earlier in life," said Dawn Trump, a 33-year-old Baltimorean who was diagnosed at age 12 on the basis of her rapid growth and other symptoms.
"We could have put a name on things -- why things had been so much different for me," she said. "It's very hard to cope with something when you don't know why" it is happening.
Ms. Trump, who is 5 feet 10 inches tall, attained that height at age 14. In her teens, she took hormones to slow her rapid growth -- at one time an inch a month -- and underwent surgery to stabilize her curving spine. In her 20s, she began taking beta blockers -- a heart medication -- to stave off the deterioration of her aorta.
Thirty-five years ago, Dr. Victor McKusick of Hopkins became the first scientist to suggest that the cluster of symptoms he began seeing in some of his heart patients -- such as long arms and a dislocated lens -- might stem from a single inherited defect in connective tissue.
Dr. McKusick, then a cardiologist, went on to become a pioneer in the study of molecular genetics. He is now a leading force behind the Human Genome Project, an international effort to map all the genes and their functions.
Last year, the answer to the mystery of Marfan drew near when Dr. Reed Pyeritz, clinical director of medical genetics at Hopkins, and a research team from Shriners identified a protein known as fibrillin as the key to Marfan syndrome.
The protein makes up a tissue that serves as a scaffolding for many of the body's organs. The scientists reported that faulty fibrillin was responsible for the structural weaknesses seen in Marfan patients.
Scientists at Shriners led by Dr. Lynn Y. Sakai then isolated the gene that produces fibrillin and figured out its structure. At Hopkins, researchers found specific genetic mutations, or defects, that cause the protein to go awry.
When they found the same mutation in two people whose Marfan had already been diagnosed on the basis of symptoms, they knew the gene was at fault. "This was the final proof that the fibrillin gene was responsible for Marfan syndrome," Dr. Dietz said.
With the new discovery, scientists have a practical way of diagnosing people who have a family history of Marfan. This is done by identifying a genetic "marker" in a family member who is known to have the disease and then determining whether it exists in other family members.
But the Hopkins scientists said they lack a practical way to screen people who want to know whether they are the first in their families ever to have the syndrome. In such a case, there is no known marker -- and no one to use for gene comparisons. Screening such patients is possible, the scientists said, but is laborious and could take days to perform and be prohibitively expensive.
It is that kind of testing that is needed to confirm suspicions, first raised in the 1960s, that the tall, gaunt appearance of Abraham Lincoln was a characteristic of Marfan syndrome. The actual investigation -- which will focus on a small blood sample from the cuff of a doctor who treated him -- will have to await refinement of the test, Dr. Dietz said.