A newborn has an absent left radius and thumb along with a secundum atrial septal defect. First-degree heart block is noted on ECG. Family history reveals the father underwent repair of an upper limb defect in infancy. What is the inheritance pattern and causative gene?

• A Autosomal recessive, TBX1
• B Autosomal recessive, HOXD13
• C Autosomal dominant, NKX2-5
• D Autosomal dominant, TBX5 ✓

Explanation

Holt-Oram syndrome is an autosomal dominant condition caused by TBX5 mutations, combining preaxial radial limb anomalies (most commonly a triphalangeal or absent thumb) with septal defects, of which secundum atrial septal defect is the most frequent. Cardiac conduction disease including first-degree atrioventricular block is typical. NKX2-5 causes isolated familial septal defects with progressive conduction block but no limb anomaly, and TBX1 is the 22q11 deletion gene.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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