We report an infant girl who was born to a 29-year-old primapara at 38 weeks' gestation. When evaluated at 3 days old, physical examination revealed a high forehead with frontal bossing, upturned nose, arched palate, shallow midface structures, and heavily ridged coronal
sutures bilaterally. Clinically, the infant seemed to be neurologically normal. Skull radiographs and computed tomography confirmed the presence of bilateral coronal
synostosis, with patency of all other
sutures. Family history was remarkable, in that the infant's father, paternal grandmother, and a paternal cousin demonstrated subtle craniofacial features, which had not been previously identified. Mutation analysis of FGFR-3 revealed a missense mutation in exon 6, c.749 C>G, with a resultant
amino acid change from
proline to
arginine at
codon 250 (P250R), in keeping with
Muenke syndrome (Am J Hum Genet 1997;60:555-564). The mutation was subsequently identified in her father, suggesting variable expression in this family, as he had only mild midfacial flattening. At 9 months of age, our patient underwent anterior cranial expansion, correction of orbital
hypertelorism, intracranial orbital
osteotomies, and advancement of the frontal bandeau. She tolerated the procedure well and has done well postoperatively.
CONCLUSIONS: We report the case of an infant with
Muenke syndrome, with evidence of variable expressivity within the paternal family. The pertinent literature, in which only 2 prior Canadian cases were identified, is reviewed.