A 3-year-old boy has recurrent sinopulmonary infections, hypocalcemic seizures, and a conotruncal heart defect (tetralogy of Fallot). Physical exam reveals a short philtrum and low-set ears. FISH demonstrates a microdeletion at 22q11.2. Which gene within this deleted region is primarily responsible for the cardiac and pharyngeal arch anomalies?
- A TBX1 ✓
- B COMT
- C DGCR8
- D CLTCL1
Correct answer: A. TBX1
Explanation
DiGeorge syndrome (22q11.2 deletion syndrome) results from failure of development of the third and fourth pharyngeal pouches. TBX1, a T-box transcription factor gene within the deleted region, is the major driver of the cardiac outflow tract defects, thymic hypoplasia, parathyroid hypoplasia, and facial anomalies. COMT, DGCR8, and CLTCL1 are also located in the 22q11.2 region but are not primarily responsible for the classic conotruncal and pharyngeal arch phenotype.
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.