A neonate has a white forelock, patchy depigmented skin, bilateral sensorineural deafness, heterochromia irides, and marked dystopia canthorum with a broad nasal root. Mutation of which gene best explains this combination?

• A GLI3
• B PAX6
• C TCOF1
• D PAX3 ✓

Explanation

Waardenburg syndrome type 1 is caused by PAX3 mutations and is distinguished from other subtypes by dystopia canthorum, reflecting PAX3 action in both the melanocyte lineage derived from neural crest and the facial skeleton. The pigmentary changes and deafness follow failure of neural crest derived melanocyte precursors to survive or migrate. PAX6 causes aniridia, GLI3 causes Pallister-Hall and Greig cephalopolysyndactyly, and TCOF1 causes Treacher Collins syndrome without pigmentation defects.

Reference: Larsen's Human Embryology, 5th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.