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

• Published in: American journal of medical genetics 2001-01, Vol.98 (1), p.75-91
• Main Authors: Schweitzer, Daniela N., Graham Jr, John M., Lachman, Ralph S., Jabs, Ethylin Wang, Okajima, Kazuki, Przylepa, Kelly A., Shanske, Alan, Chen, Kelly, Neidich, Julie A., Wilcox, William R.
• Format: Article
• Language: English
• Subjects: acanthosis nigricans; Acanthosis Nigricans - etiology; Acanthosis Nigricans - genetics; Achondroplasia - complications; Achondroplasia - diagnosis; Achondroplasia - diagnostic imaging; Achondroplasia - genetics; Amino Acid Substitution - genetics; Biological and medical sciences; choanal atresia; Craniofacial Dysostosis - complications; Craniofacial Dysostosis - genetics; craniosynostosis; Crouzon syndrome; Diseases of the osteoarticular system; Female; FGFR3; fibroblast growth factor receptor 3; Humans; hydrocephalus; Infant, Newborn; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Protein-Tyrosine Kinases; Radiography; Receptor, Fibroblast Growth Factor, Type 3; Receptors, Fibroblast Growth Factor - genetics
• ISSN: 0148-7299; 1096-8628
• DOI: 10.1002/1096-8628(20010101)98:1<75::AID-AJMG1010>3.0.CO;2-6

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, individuals with this disorder have craniosynostosis, ocular proptosis, midface hypoplasia, choanal atresia, hydrocephalus, and they experience the onset of acanthosis nigricans during childhood. We report three cases and compare the 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, we carefully reviewed the skeletal findings in six patients. We identified subtle radiographic findings of achondroplasia in all six cases including narrow sacrosciatic notches, short vertebral bodies, lack of the normal increase in interpediculate distance from the upper lumbar vertebrae caudally, and broad, short metacarpals and phalanges. Even before acanthosis nigricans appears, the presence of choanal atresia and hydrocephalus in an individual with features of Crouzon syndrome should suggest the diagnosis of CAN, and subtle skeletal findings can lend further support to this diagnosis. © 2001 Wiley‐Liss, Inc.