关键词: 　心-面-皮肤综合征；　BRAF基因；　二代测序技术；　表型

Abstract: 　Objective　To investigate the clinical manifestations and genetic features of two patients with severe cardiofacio-cutaneous syndrome. Methods　High throughput sequencing was applied to detect the genetic change of two children with severe cardio-facio-cutaneous syndrome. The clinical manifestations and genetic characteristics were analyzed, and literature was reviewed. Results　Both of the two patients had severe feeding problems, mental retardation and motor delays after birth. Besides the typical craniofacial features and cardiac malformations, laryngotracheal abnormalities were observed. Both patients died before six months old. Genetic detection revealed de novo heterogenous mutations in BRAF gene (1783T>C, p.F595L and c.770A>G, p.Q257R). Conclusion　This is the first report of severe cardio-facio-cutaneous syndrome caused by BRAF gene mutation in China, coupled with features such as severe neurologic abnormalities, gastrointestinal symptoms and laryngotracheal abnormalities. The prognosis is poor.

Key words: 　cardio-facio-cutaneous syndrome;　BRAF gene;　next-generation sequencing;　phenotype