Public Release: 

Researchers Find Genetic Clues To Intestinal Disease

Johns Hopkins Medicine

In a series of recently published studies, Johns Hopkins researchers have shown that an intestinal disease affecting 400,000 people in the United States is actually a variety of related disorders that can be inherited and cause similar symptoms in close relatives. The findings will help physicians predict who will get the disease, called Crohn's disease, speed diagnosis, and help determine the best treatment for each individual.

"Although earlier studies had suggested that Crohn's disease might be several distinct disorders, this is the first large study of a group of families that confirms those suggestions," says Theodore M. Bayless, M.D., professor of medicine and gastroenterology.

The findings have prompted Bayless and his co-worker, Steven Brant, M.D., to encourage people with a family history of Crohn's disease to participate in a Hopkins study to identify the genes responsible for the disease.

Crohn's disease, which causes painful inflammation of the intestine and severe diarrhea, may appear in one of three forms: 1) a relatively mild form that remains localized in one area of the intestine; 2) intestinal scarring that eventually causes blockage of the intestine; and 3) a more dangerous form that sometimes perforates the intestinal wall.

In one study, published in the March issue of Lancet, the researchers found that the disease occurs earlier in life in people whose parents also have a history of Crohn's disease. This type of earlier onset of a more severe form of a hereditary disease in the child than in the parent is called genetic anticipation.

The study is the first to show genetic anticipation in a disorder caused by multiple genes, according to Bayless. The Hopkins team speculated that the disease, which is probably caused by mutations in several yet unidentified genes, may be made worse when there are numerous copies of these mutations, called a triplet repeat.

"Our finding of genetic anticipation in Crohn's disease will help researchers look for the genes responsible for the disease and help identify those at risk for developing it," says Bayless.

In a related study in the September issue of Gastroenterology, the Hopkins researchers found that, although the disease can cause a variety of symptoms, it tends to strike the same part of the intestine and cause the same symptoms in close relatives who have inherited the disease. This suggests the disease is actually several different disorders, each one of which is presumably inherited separately, says Bayless.

"The finding is important because there are different treatment options for Crohn's disease," says Bayless. "Knowing which type a patient has will help us determine quickly which treatment should work best for each patient."

Crohn's disease can be treated with medication, but two-thirds of people affected need surgery, usually because of a blockage in the intestine. And in half of these cases, the disease returns after the operation.

In the study published in Lancet, Bayless and his co-workers studied the hospital records of 552 patients treated for Crohn's disease at Johns Hopkins. They found the disease in 27 pairs of first-degree relatives, for example, father and son or brother and sister. Another 32 such pairs of patients were identified through a multi-center survey.

Among the Hopkins patients, the younger of each pair developed Crohn's disease an average of about 11 years earlier in life than the older one. Among the multi-center patients, younger members of pairs of Crohn's disease patients developed the disease about 15 years earlier. In addition, the disease was more serious in the offspring than in the parent for 15 of the 27 Hopkins pairs. And in 13 of those pairs, the affected parent was the father.

In the studies published in Gastroenterology, the Hopkins team reported that among families of 60 patients, 86 percent of the families had at least two members with the disease in the same area of the intestine. And in 82 percent of cases, family members had the same form of the disease.

"This suggests that there are different genes responsible for the different forms of the disease," says Bayless.

The team also reported in Gastroenterology that Crohn's disease patients who were younger than 20 years when diagnosed were more likely to have a family history of Crohn's disease, more problems in the small intestine, more stricturing disease and require more surgery than patients 40 years and older.

The other authors of the reports are Joseph M. Polito II, Renee C. Rees, Barton Childs, Albert I. Mendeloff, Mary L. Harris, Arron Z. Tokayer, Shirley A. Quaskey, and E. David Mellitis.

Individuals who want to participate in the Crohn's disease family studies at Johns Hopkins can get more information by calling (410) 614-1982.


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