Familial patent ductus arteriosus and bicuspid aortic valve with hand anomalies: A novel heart-hand syndrome

The association between cardiac and limb defects, particularly those affect ing the hand, has been well documented by the delineation of several heart- hand syndromes, Based on observations with a three-generation family with s even affected individuals, we describe a novel heart-hand syndrome comprisi ng patent ductus arteriosus, bicuspid aortic valve, 5th metacarpal hypoplas ia, and brachydactyly. The inheritance pattern was consistent with autosoma l dominance, although X-linked dominance could not be excluded. Penetrance appeared to be complete, but there was variability of the cardiac and hand phenotypes, Because this new syndrome closely resembled Char syndrome (pate nt ductus arteriosus, 5th finger middle phalangeal hypoplasia, and minor fa cial anomalies), multipoint linkage analysis was performed using polymorphi c DNA markers spanning the recently identified Char syndrome critical regio n at chromosomal bands 6p12-p21.1. This analysis formally excluded this 3-c M region, documenting that the two traits are not allelic, In sum, a novel heart-hand syndrome involving left ventricular outflow and aortic arch as w ell as an ulnar ray derivative has been identified, Because the hand anomal ies can be subtle, thorough evaluation is suggested for families inheriting these cardiac defects as a mendelian trait. (C) 1999 Wiley-Liss, Inc.