BACKGROUND:

Familial hypertrophic cardiomyopathy is a disease of heart muscle that is genetically transmitted as an autosomal dominant trait, with a high degree of penetrance. Affected individuals typically have asymmetric thickening of the interventricular septum often involving the adjacent left ventricular free wall. Histologically, myocardial cells are enlarged and muscle bundles are grossly disorganized, producing a whorled pattern. The physiologic consequence of this cardiomyopathy is diastolic dysfunction with impaired ventricular relaxation and elevated diastolic pressures in the heart and pulmonary vasculature. Patients can experience dyspnea, angina, palpitations, and syncope. Complications of the disease include atrial fibrillation, congestive heart failure, thromboembolism, and most importantly, sudden death.

DESIGN NARRATIVE:

The three kindreds studied included one in Iceland, one in the St. Lawrence region in Canada, and one in the Pittsburgh, Pennsylvania area.

Pedigrees were established for the three kindreds. All family members were clinically evaluated by physical exam, electrocardiogram, and comprehensive M-mode and two-dimensional echocardiography. Lymphoblastoid cell lines were derived from all members of the three pedigrees. Restriction fragment length polymorphism analyses were used to identify a DNA probe that was linked to familial hypertrophic cardiomyopathy. Studies were conducted to determine if the familial hypertrophic cardiomyopathy locus was the same in all three kindreds and to identify the gene responsible.