A 4-year-old girl is referred after a murmur was heard. Echocardiography shows an ostium secundum atrial septal defect. Her right thumb is triphalangeal and hypoplastic. Her father has similar thumb anomalies. What is the underlying genetic defect?

• A Mutation in NKX2-5
• B Deletion of 22q11.2
• C Mutation in TBX5 ✓
• D Trisomy of chromosome 13

Explanation

Holt-Oram syndrome is an autosomal dominant condition caused by mutations in TBX5, a transcription factor critical for cardiac septation and upper limb development. It combines an ostium secundum atrial septal defect, the commonest lesion, with radial ray anomalies ranging from a triphalangeal or hypoplastic thumb to complete radial aplasia. Isolated familial ASD can involve NKX2-5 but lacks skeletal anomalies, and trisomy 13 produces polydactyly rather than radial thumb defects.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.