A newborn girl has bilateral absent thumbs and an ostium secundum atrial septal defect on echocardiography with first-degree AV block on ECG. The underlying mutation involves:

• A NKX2-5 gene
• B TBX5 gene ✓
• C GATA4 gene
• D PTPN11 gene

Explanation

Holt-Oram syndrome is an autosomal dominant disorder caused by mutations in TBX5, a transcription factor essential for forearm and cardiac septation development. It produces radial ray defects such as absent, hypoplastic, or triphalangeal thumbs combined with a secundum ASD and varying degrees of AV conduction block. NKX2-5 and GATA4 cause familial ASD without limb anomalies, and PTPN11 causes Noonan syndrome with pulmonary stenosis and short stature.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.