AUTOSOMAL-DOMINANT MARFAN-LIKE CONNECTIVE-TISSUE DISORDER WITH AORTICDILATION AND SKELETAL ANOMALIES NOT LINKED TO THE FIBRILLIN GENES

We describe a large family with a connective-tissue disorder that exhi bits some of the skeletal and cardiovascular features seen in Marfan s yndrome. However, none of the 19 affected individuals displayed ocular abnormalities and therefore did not comply with recognized criteria f or this disease. These patients could alternatively be diagnosed as MA SS (mitral valve, aorta, skeleton, and skin) phenotype patients or rep resent a distinct clinical entity, i.e., a new autosomal dominant conn ective-tissue disorder. The fibrillin genes located on chromosomes 15 and 5 are clearly involved in the classic form of Marfan syndrome and a clinically related disorder (congenital contractural arachnodactyly) , respectively. To test whether one of these genes was also implicated in this French family, we performed genetic analyses. Blood samples w ere obtained for 56 family members, and four polymorphic fibrillin gen e markers, located on chromosomes 15 (Fib15) and 5 (Fib5), respectivel y, were tested. Linkage between the disease allele and the markers of these two genes was excluded with lod scores of -11.39 (for Fib15) and -13.34 (for Fib5), at theta = .001, indicating that the mutation is a t a different locus. This phenotype thus represents a new connective-t issue disorder, overlapping but different from classic Marfan syndrome .