Subtle radiographic findings of achondroplasia in patients with Crouzon syndrome with acanthosis nigricans due to an Ala391Glu substitution in FGFR3

A unique type of craniofacial dysostosis, Crouzon syndrome with acanthosis nigricans (CAN), has been attributed to a specific substitution (Ala391Glu) in the fibroblast growth factor receptor 3 (FGFR3) gene. At birth, individ uals with this disorder have craniosynostosis, ocular proptosis, midface hy poplasia, choanal atresia, hydrocephalus, and they experience the onset of acanthosis nigricans during childhood. We report three cases and compare th e clinical characteristics of our cases with the previously reported cases of this disorder. Since the Ala391Glu substitution in FGFR3 is close to the substitutions in the transmembrane domain that result in achondroplasia, w e carefully reviewed the skeletal findings in six patients. We identified s ubtle radiographic findings of achondroplasia in all six cases including na rrow sacrosciatic notches, short vertebral bodies, lack of the normal incre ase in interpediculate distance from the upper lumbar vertebrae caudally, a nd broad, short metacarpals and phalanges. Even before acanthosis nigricans appears, the presence of choanal atresia and hydrocephalus in an individua l with features of Crouzon syndrome should suggest the diagnosis of CAN, an d subtle skeletal findings can lend further support to this diagnosis. Am. J. Med. Gen. 98:75-91, 2001. (C) 2001 Wiley-Liss, Inc.