A term newborn has severe microcephaly, hypotelorism, and a single midline cerebral ventricle with fused thalami. Mutations in which gene are the most common known genetic cause of this spectrum?
- A FGF8
- B WNT3
- C SHH ✓
- D PAX6
Correct answer: C. SHH
Explanation
Holoprosencephaly results from failed cleavage of the prosencephalon into two hemispheres, and SHH is its most frequently implicated gene because midline SHH from the prechordal plate and ventral forebrain drives medial-lateral patterning of the brain and face. PAX6 governs eye and cortical development but is linked to aniridia rather than holoprosencephaly. Other recognised HPE genes include ZIC2 and SIX3, but SHH remains the classic answer.
Reference: Langman's Medical Embryology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.