title: Variable expressivity of pfeiffer syndrome in a family with FGFR1 p.Pro252Arg mutation.
abstract: Pfeiffer syndrome is an autosomal dominant disorder classically characterized by craniosynostosis, facial dysmorphism and limb anomalies. The majority of cases are caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. A specific, rare mutation p.Pro252Arg, located between the second and third extracellular immunoglobulin-like domain of FGFR1, is associated with mild clinical signs. We report on a three-generation family with five members having a heterozygous FGFR1 p.Pro252Arg mutation. Phenotypic features within the family showed high variability from the apparently normal skull and limbs to the characteristic brachycephaly and digital anomalies. The typical features of Pfeiffer syndrome appeared only in the third generation allowing us to unveil the syndrome in several further family members in two previous generations. Variable expressivity can complicate the recognition of Pfeiffer syndrome, principally the mild type 1, requiring careful phenotyping and genetic counseling.
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Beáta
authors.initials: B
authors.lastname: Bessenyei
authors.forename: Mariann
authors.initials: M
authors.lastname: Tihanyi
authors.forename: Marianna
authors.initials: M
authors.lastname: Hartwig
authors.forename: Katalin
authors.initials: K
authors.lastname: Szakszon
authors.forename: Éva
authors.initials: É
authors.lastname: Oláh
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D006814:Hungary; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*
chemical_list: C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: FGFR1; Pfeiffer syndrome; clinodactyly; craniosynostosis; syndactyly