title: Central nervous system malformations and deformations in FGFR2-related craniosynostosis.
abstract: Central nervous system anomalies in Pfeiffer syndrome (PS) due to mutations in the FGFR2 gene are poorly understood, even though PS is often associated with serious cognitive impairment. The aim of this study is to describe the neuropathological phenotype in PS. We present four severe fetal cases of sporadic PS with FGFR2 mutations who underwent termination followed by fetopathological and neuropathological examination. We studied the expression pattern of Fgfr2 in the mouse brain using radioactive fluorescence in situ hybridization. PS is associated with brain deformations due to the abnormal skull shape, but FGFR2 mutations also induce specific brain developmental anomalies: megalencephaly, midline disorders, amygdala, and hippocampus malformations, and ventricular wall alterations. The expression pattern of Fgfr2 in mice matches the distribution of malformations in humans. The brain anomalies in PS result from the combination of mechanical deformations and intrinsic developmental disorders due to FGFR2 hyperactivity. Several similarities are noted between these anomalies and the brain lesions observed in other syndromes due to mutations in FGF-receptor genes. The specific involvement of the hippocampus and the amygdala should encourage the precise cognitive screening of patients with mild forms of PS.
authors.affiliation: Craniofacial Development and Stem Cell Biology, Comprehensive Biomedical Research Centre, Dental Institute, King's College London, Guy's Hospital, London, United Kingdom. roman.khonsari@kcl.ac.uk
authors.forename: Roman Hossein
authors.initials: RH
authors.lastname: Khonsari
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Wenfei
authors.initials: W
authors.lastname: Kang
authors.forename: Jean M
authors.initials: JM
authors.lastname: Hébert
authors.forename: Bettina
authors.initials: B
authors.lastname: Bessières
authors.forename: Valérie
authors.initials: V
authors.lastname: Bodiguel
authors.forename: Catherine
authors.initials: C
authors.lastname: Collet
authors.forename: Laurence
authors.initials: L
authors.lastname: Legeai-Mallet
authors.forename: Paul T
authors.initials: PT
authors.lastname: Sharpe
authors.forename: Catherine
authors.initials: C
authors.lastname: Fallet-Bianco
mesh_terms: D037881:Aborted Fetus; D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D003398:Craniosynostoses / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D056726:Genetic Association Studies; D006801:Humans; D051379:Mice; D009154:Mutation; D010641:Phenotype; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D051497:Receptor, Fibroblast Growth Factor, Type 2