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Holt-Oram syndrome (HOS) is characterized by mild-to-severe congenital cardiac defects and skeletal abnormalities of the upper limbs. The most common cardiac disorder is an ostium secundum atrial septal defect (ASD), followed by ventricular septal defect (VSD) and ostium primum ASD. Electrocardiographical abnormalities such as various degrees of atrioventricular block have also been reported. In addition hypoplastic peripheral vessels of the upper limbs have been observed. Frequent orthopedic signs are radial ray abnormalities, absent or abnormal radius, upper limb-transverse elements missing and various thumb anomalies. One out of 100,000 live births is affected. More than 300 cases have been published, revealing a wide spectrum of clinical signs. HOS is an autosomal dominant disorder with complete penetrance. The underlying genetic defect was found on the long arm of chromosome 12 (12q2). Mutations in the TBX3 and TBX5 genes lead to a wide range of phenotypes. Echocardiography can be used to detect cardiac anomalies in the offspring of a parent with HOS. Genetic counseling is recommended. Surgical operation can be performed in order to treat ASD. |