Genetic analysis of young adult patients with aortic disease not fulfilling the diagnostic criteria for Marfan syndrome.

BACKGROUND: Although the existence of the young patients with aortic disease not fulfilling the diagnostic criteria for Marfan syndrome (MFS) has been known, the etiology of their disease has not yet been elucidated. The purpose of the present study was to elucidate the genetic and clinical features of the young patients with aortic disease not having MFS.

METHODS AND RESULTS: Eighty young adult patients with aortic disease were examined. They were divided into a definite MFS (n=51) and a non-definite MFS group (n=29) according to the Ghent nosology. Clinical and genetic characteristics were compared between the 2 groups. Among 29 non-definite MFS probands, 1 (3%) FBN1, 2 (7%) TGFBR1, and 3 (10%) TGFBR2 mutations were found, and 4 ACTA2 mutations were found in the 23 probands examined without FBN1, TGFBR1, or TGFBR2 mutations. In total, more than 10 out of 29 (34%) probands in the non-definite MFS group were associated with genetic mutations. Skeletal involvement was less frequent in the non-definite than in the definite MFS group (7% vs 82%, P<0.01).

CONCLUSIONS: In the probands with aortic diseases in young who cannot be diagnosed with MFS, mutations other than FBN1 mutations accounted for at least one-third of all causes of aortic disease.