A term newborn has severe microcephaly with a single midline cerebral ventricle (alobar holoprosencephaly), hypotelorism, and a flattened nasal bridge. Chromosomal analysis is normal. Mutation of which gene is the most likely cause?
- A PAX3
- B SHH ✓
- C TBX1
- D NKX2-5
Correct answer: B. SHH
Explanation
SHH secreted by the prechordal plate and notochord induces the ventral forebrain and separates the cerebral hemispheres and optic vesicles. Loss-of-function mutations of SHH produce holoprosencephaly with hypotelorism and midline facial defects. PAX3 mutations cause Waardenburg syndrome with neural crest defects, and TBX1 deletions cause the conotruncal and thymic defects of 22q11 deletion, neither of which produces a single fused ventricle.
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.