Craniosynostosis in patients with RASopathies: Accumulating clinical evidence for expanding the phenotype.
Craniosynostosis in patients with RASopathies: Accumulating clinical evidence for expanding the phenotype.
复制标题
RASopathies 患者的颅缝早闭：为扩大表型积累临床证据。
DOI：
10.1002/ajmg.a.38337
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Okamoto N.
中科院分区：
文献类型：
--
作者：
Ueda K;Yaoita M;Niihori T;Aoki Y;Okamoto N.
RAS病是由RAS/丝裂原活化蛋白激酶（MAPK）信号通路失调引起的表型重叠遗传性疾病。RASopathy包括努南综合征、心面皮肤（CFC）综合征、Costello综合征、1型神经纤维瘤病、Legius综合征、努南综合征伴多发性雀斑、努南样综合征、遗传性牙龈纤维瘤病和毛细血管畸形/动静脉畸形综合征。最近，6例颅缝早闭和努南综合征患者涉及KRAS突变的综述中描述，1例颅缝早闭和努南综合征患者涉及SHOC 2突变也已报道。在此，我们描述了PTPN 11基因的新发突变导致的颅缝早闭和努南综合征患者，以及BRAForKRAS基因的新发突变导致的颅缝早闭和CFC综合征患者。除了CFC综合征和努南综合征的典型表型外，所有这些患者都有颅骨畸形。在RASopathy中，有颅骨畸形的患者，可能需要进一步评估以寻找颅缝早闭。未来的研究应试图阐明RAS/MAPK信号通路介导的颅缝早闭的致病机制。
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 involvingKRASmutations were described in a review, and a patient with craniosynostosis and Noonan syndrome involving aSHOC2mutation has also been reported. Here, we describe patients with craniosynostosis and Noonan syndrome due to de novo mutations inPTPN11and patients with craniosynostosis and CFC syndrome due to de novo mutations inBRAForKRAS. 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.