Craniosynostosis in patients with RASopathies: Accumulating clinical evidence for expanding the phenotype

Kimiko Ueda, Masako Yaoita, Tetsuya Niihori, Yoko Aoki, Nobuhiko Okamoto

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

RASopathies are phenotypically overlapping genetic disorders caused by dysregulation of the RAS/mitogen-activated protein kinase (MAPK) signaling pathway. RASopathies include Noonan syndrome, cardio-facio-cutaneous (CFC) syndrome, Costello syndrome, Neurofibromatosis type 1, Legius syndrome, Noonan syndrome with multiple lentigines, Noonan-like syndrome, hereditary gingival fibromatosis, and capillary malformation/arteriovenous malformation syndrome. Recently, six patients with craniosynostosis and Noonan syndrome involving KRAS mutations were described in a review, and a patient with craniosynostosis and Noonan syndrome involving a SHOC2 mutation has also been reported. Here, we describe patients with craniosynostosis and Noonan syndrome due to de novo mutations in PTPN11 and patients with craniosynostosis and CFC syndrome due to de novo mutations in BRAF or KRAS. All of these patients had cranial deformities in addition to the typical phenotypes of CFC syndrome and Noonan syndrome. In RASopathy, patients with cranial deformities, further assessments may be necessary to look for craniosynostosis. Future studies should attempt to elucidate the pathogenic mechanism responsible for craniosynostosis mediated by the RAS/MAPK signaling pathway.

Original languageEnglish
Pages (from-to)2346-2352
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume173
Issue number9
DOIs
Publication statusPublished - 2017 Sep

Keywords

  • Noonan syndrome
  • RASopathy
  • cardio-facio-cutaneous syndrome
  • craniosynostosis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'Craniosynostosis in patients with RASopathies: Accumulating clinical evidence for expanding the phenotype'. Together they form a unique fingerprint.

Cite this