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Variable expressivity of pfeiffer syndrome in a family with FGFR1 p.Pro252Arg mutation
Author(s) -
Bessenyei Beáta,
Tihanyi Mariann,
Hartwig Marianna,
Szakszon Katalin,
Oláh Éva
Publication year - 2014
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36774
Subject(s) - craniosynostosis , fibroblast growth factor receptor 1 , genetics , expressivity , crouzon syndrome , short stature , mutation , biology , fibroblast growth factor , gene , endocrinology , receptor
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. © 2014 Wiley Periodicals, Inc.