Variable clinical expression of Holt-Oram syndrome in three generations

Holt-Oram syndrome is a distinct autosomal dominant entity presenting with upper limb defects and cardiac abnormality. No correlation between the severity of the heart and the limb defects has been established. Here we report variable clinical expression of Holt-Oram syndrome in three generations. The grandfather presented with typical upper limb defects: phocomelia of arms with three digits on each hand, congenital heart defect and narrow shoulders. His son manifested cardiac conduction disturbance with no congenital heart or skeletal defect. The granddaughter showed ventricular septal defect and moderate radial deviations of both hands with no obvious hypoplasia of the extremities. Clinical data of the presented family suggests lack of penetrance with respect to skeletal and structural cardiac abnormalities in the Holt-Oram syndrome.