Holt-Oram Syndrome

Holt-Oram Syndrome is a familial heart disease with skeletal malformations described by Mary Holt and Samuel Oram. Initial description was familial atrial septal defect associated with abnormalities of the radial aspect of the upper limb. Characteristic abnormality was the simian thumb which lies in the same plane as the other fingers and hence unable to oppose like a normal thumb. Holt-Oram Syndrome has also been called as atriodigital dysplasia, though ventricular septal defect and other cardiac abnormalities were reported later. The semial report had described associated conduction disturbances and arrhythmias as well.

Autosomal dominant inheritance has been associated with mutation in transcription factor gene TBX5 in Holt-Oram syndrome. Cardiac malformations are seen in 75% of affected family members. Carpal bone abnormalities are clinically silent and evident only radiologically. Due to the autosomal dominant pattern of inheritance, 50% of offspring can be affected. TBX5 mutations account for upto 70% of cases of Holt-Oram syndrome. Nearly 85% of cases of Holt-Oram Syndrome have de novo mutations.