Abstract: Objective　To explore the clinical phenotype and gene variation features of Cardio-facio-cutaneous syndrome (CFC). Method　DNA were extracted from peripheral blood in 2 children with CFC and their parents, and the mutation gene were detected by high throughput sequencing of target gene and verified by Sanger sequencing. Results　Two patients were Han nationality females and aged 13 months and 7.5years respectively. Both of them showed craniofacial features of epicanthus, flat nose and scant hair, and had history of growth retardation and epileptic seizure. The electrocardiogram in one case showed that there was a change in T wave and P-R interval reached the normal high limit. The electrocardiogram in the other case was normal. Genetic detection revealed that there were two heterozygous missense mutation in the third exon of MAP2K1, c.383G>T, p.Gly128Val and c.389A>G, p.Tyr130Cys, which were new mutations (de novo) and CFC mutation sites reported in the literature. Conclusion　The two cases of CFC were first reported in China and both had MAP2K1 mutations. The children with CFC were reported to be mostly complicated with heart disease, thus these 2 patients should be followed up for cardiac function.