Phenotype of the fibroblast growth factor receptor 2 Ser351Cys mutation: Pfeiffer syndrome type III

• Published in: American journal of medical genetics 1998-07, Vol.78 (4), p.356-360
• Main Authors: Gripp, Karen W., Stolle, Catherine A., McDonald-McGinn, Donna M., Markowitz, Richard I., Bartlett, Scott P., Katowitz, James A., Muenke, Maximilian, Zackai, Elaine H.
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - genetics; Acrocephalosyndactylia - diagnostic imaging; Acrocephalosyndactylia - genetics; Amino Acid Substitution - genetics; Biological and medical sciences; Complex syndromes; craniosynostosis; Cysteine - genetics; Elbow - abnormalities; Elbow - diagnostic imaging; elbow ankylosis; Eye Abnormalities - genetics; fibroblast growth factor receptor 2; Foot Deformities, Congenital - diagnostic imaging; Foot Deformities, Congenital - genetics; Hand Deformities, Congenital - diagnostic imaging; Hand Deformities, Congenital - genetics; Humans; hydrocephalus; Infant, Newborn; Male; Medical genetics; Medical sciences; Pfeiffer syndrome type III; Phenotype; Point Mutation; Polymorphism, Single-Stranded Conformational; proptosis; Radiography; Receptor Protein-Tyrosine Kinases - genetics; Receptor, Fibroblast Growth Factor, Type 2; Receptors, Fibroblast Growth Factor - genetics; Ser351Cys; Serine - genetics; Translocation, Genetic; Wheelchairs
• ISSN: 0148-7299; 1096-8628
• DOI: 10.1002/(SICI)1096-8628(19980724)78:4<356::AID-AJMG10>3.0.CO;2-H

We present a patient with pansynostosis, hydrocephalus, seizures, extreme proptosis with luxation of the eyes out of the lids, apnea and airway obstruction, intestinal nonrotation, and severe developmental delay. His skeletal abnormalities include bilateral elbow ankylosis, radial head dislocation, and unilateral broad and deviated first toe. The phenotype of this patient is consistent with that previously reported in Pfeiffer syndrome type III, but is unusual for the lack of broad thumbs. Our patient most closely resembles the case described by Kerr et al. [1996: Am J Med Genet 66:138–143] as Pfeiffer syndrome type III with normal thumbs. Mutations in the genes for fibroblast growth factor receptors (FGFR) 1 and 2 have previously been seen in patients with Pfeiffer syndrome type I. The mutation identified in our patient, Ser351Cys in FGFR2, represents the first reported cause of Pfeiffer syndrome type III. An identical mutation was described once previously by Pulleyn et al., in a patient whose brief clinical description included cloverleaf skull, significant developmental delay, and normal hands and feet [Eur. J. Hum. Genet. 4:283–291, 1996]. In our patient, previously performed single‐strand conformation polymorphism analysis failed to detect a band shift; the mutation was identified only after independent sequence analysis. Am. J. Med. Genet. 78:356–360, 1998. © 1998 Wiley‐Liss, Inc.