title: A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.
abstract: The underlying basis of many forms of syndromic craniosynostosis has been defined on a molecular level. However, many patients with familial or sporadic craniosynostosis do not have the classical findings of those craniosynostosis syndromes. Here we present 61 individuals from 20 unrelated families where coronal synostosis is due to an amino acid substitution (Pro250Arg) that results from a single point mutation in the fibroblast growth factor receptor 3 gene on chromosome 4p. In this instance, a new clinical syndrome is being defined on the basis of the molecular finding. In addition to the skull findings, some patients had abnormalities on radiographs of hands and feet, including thimble-like middle phalanges, coned epiphyses, and carpal and tarsal fusions. Brachydactyly was seen in some cases; none had clinically significant syndactyly or deviation of the great toe. Sensorineural hearing loss was present in some, and developmental delay was seen in a minority. While the radiological findings of hands and feet can be very helpful in diagnosing this syndrome, it is not in all cases clearly distinguishable on a clinical basis from other craniosynostosis syndromes. Therefore, this mutation should be tested for in patients with coronal synostosis.
authors.affiliation: Department of Pediatrics, University of Pennsylvania, Philadelphia, USA. muenke@mail.med.upenn.edu
authors.forename: M
authors.initials: M
authors.lastname: Muenke
authors.forename: K W
authors.initials: KW
authors.lastname: Gripp
authors.forename: D M
authors.initials: DM
authors.lastname: McDonald-McGinn
authors.forename: K
authors.initials: K
authors.lastname: Gaudenz
authors.forename: L A
authors.initials: LA
authors.lastname: Whitaker
authors.forename: S P
authors.initials: SP
authors.lastname: Bartlett
authors.forename: R I
authors.initials: RI
authors.lastname: Markowitz
authors.forename: N H
authors.initials: NH
authors.lastname: Robin
authors.forename: N
authors.initials: N
authors.lastname: Nwokoro
authors.forename: J J
authors.initials: JJ
authors.lastname: Mulvihill
authors.forename: H W
authors.initials: HW
authors.lastname: Losken
authors.forename: J B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: A E
authors.initials: AE
authors.lastname: Guttmacher
authors.forename: R S
authors.initials: RS
authors.lastname: Wilroy
authors.forename: L A
authors.initials: LA
authors.lastname: Clarke
authors.forename: G
authors.initials: G
authors.lastname: Hollway
authors.forename: L C
authors.initials: LC
authors.lastname: Adès
authors.forename: E A
authors.initials: EA
authors.lastname: Haan
authors.forename: J C
authors.initials: JC
authors.lastname: Mulley
authors.forename: M M
authors.initials: MM
authors.lastname: Cohen
authors.forename: G A
authors.initials: GA
authors.lastname: Bellus
authors.forename: C A
authors.initials: CA
authors.lastname: Francomano
authors.forename: D M
authors.initials: DM
authors.lastname: Moloney
authors.forename: S A
authors.initials: SA
authors.lastname: Wall
authors.forename: A O
authors.initials: AO
authors.lastname: Wilkie
mesh_terms: D000328:Adult; D002648:Child; D002894:Chromosomes, Human, Pair 4; D003398:Craniosynostoses / Q000235:genetics*; D005260:Female; D005532:Foot Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D006228:Hand Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases; D011859:Radiography; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D013577:Syndrome
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3