Central nervous system malformations and deformations in FGFR2-related craniosynostosis

Roman Hossein Khonsari, Anne Lise Delezoide, Wenfei Kang, Jean M. Hébert, Bettina Bessières, Valérie Bodiguel, Catherine Collet, Laurence Legeai-Mallet, Paul T. Sharpe, Catherine Fallet-Bianco

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2797-2806
Number of pages10
JournalAmerican Journal of Medical Genetics, Part A
Volume158 A
Issue number11
StatePublished - Nov 2012


  • Central nervous system
  • Craniosynostosis
  • FGFR
  • Intellectual disability
  • Pfeiffer syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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