A newborn has a single midline cerebral ventricle, fused basal ganglia, hypotelorism and midline facial clefting. Reduced activity of which morphogen during early forebrain development best explains this presentation?

• A Nodal from the visceral endoderm
• B Bone morphogenetic protein 4 from the roof plate
• C Retinoic acid from the somites
• D Sonic hedgehog from the prechordal plate ✓

Explanation

Holoprosencephaly reflects failed cleavage of the prosencephalon into two hemispheres. Prechordal plate SHH is required for midline forebrain division; loss-of-function SHH variants, or inhibition by cholesterol biosynthesis defects such as Smith-Lemli-Opitz syndrome, produce this spectrum. BMP4 patterns dorsal neural structures, and retinoic acid posteriorises hindbrain segments, so neither accounts for the midline forebrain fusion.

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.