A newborn is noted to have craniosynostosis with a cloverleaf skull, midface hypoplasia, proptosis, and broad great toes. CT confirms premature fusion of multiple sutures. Which gene mutation is most likely responsible?
- A FGFR2 ✓
- B FGFR1
- C TWIST1
- D FBN1
Correct answer: A. FGFR2
Explanation
Cloverleaf skull (Kleeblattschädel) in a neonate with craniosynostosis, midface hypoplasia, proptosis, and broad great toes is classic for Pfeiffer syndrome type 2 or severe Crouzon syndrome. Both are caused by FGFR2 mutations. FGFR1 causes Pfeiffer syndrome type 1 (milder). TWIST1 mutations cause Saethre-Chotzen syndrome. FBN1 causes Marfan syndrome, which does not involve craniosynostosis.
Reference: Smith's Recognizable Patterns of Human Malformation, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.