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

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.

Source: American Journal of Medical Genetics Part A - June 26, 2017 Category: Genetics & Stem Cells Authors: Kimiko Ueda, Masako Yaoita, Tetsuya Niihori, Yoko Aoki, Nobuhiko Okamoto Tags: ORIGINAL ARTICLE Source Type: research