A term newborn has microcephaly, a single midline ventricle, fused thalami, and hypotelorism. MRI confirms absence of separation of the cerebral hemispheres. Mutation of which secreted signalling molecule is the most likely cause?

• A Fibroblast growth factor 8 (FGF8)
• B Bone morphogenetic protein 4 (BMP4)
• C Wnt7a
• D Sonic hedgehog (SHH) ✓

Explanation

SHH from the prechordal plate and notochord induces the ventral forebrain and separates the paired optic vesicles and cerebral hemispheres. Loss-of-function SHH mutations cause holoprosencephaly with a spectrum from cyclopia to milder midline defects. BMP4, Wnt7a and FGF8 pattern other axes: Wnt7a governs dorsoventral limb polarity, FGF8 acts at the isthmus and AER, and none of these is linked to midline forebrain cleavage.

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.