Abstract:

objective: To investigate the clinical and genetic features of Kabuki syndrome caused by KMT2D mutation and summarize the clinical features in neonate. Methods: Using Whole-Exome Sequencing (WES) and Clinical panel deep sequencing，combined with data analysis pipeline established by molecular diagnostic center of Children's Hospital of Fudan University, the clinical and molecular features of 6 children with KMT2D mutations were summarized. Databases including PubMed，CNKI，WanFang Database and VIP were searched to collect literature of KS, which describe the clinical features of neonatal period from April 2012 to April 2017. Results: Four males and two females were diagnosed as KS. Three cases were diagnosed by WES due to KS related manifestations were present and the families came to order trio-WES. One case was diagnosed by clinical neonatal panel screening. Another two cases were diagnosed by WES. Seven heterozygous mutations were detected in six patients with KS，mutations were located in exon 11, exon 39, exon 51 and exon 53 respectively. The types of mutations were one stop gained, four missenses and two frameshifts. Mutation of c.12697C>T（p.Q4233X）、c.16498C>T（p.R5500W）、c.16273G>A（p.E5425K）were reported as pathogenic mutations and had recorded in Human Gene Mutation Database (HGMD). Mutation of c.12696G>T(p.Q4232H), c.3495delC (p.Pro1165LeufsTer47), c.10881delT （p.Leu3627Argfs Ter31）and c.12560G>A（p.G418E）were novel, which predicted as harmful variants by SIFT, polyphen 2 and MutationTaster software. In a total of 18 literatures，together with the 2 cases in this study, there were 34 neonates were included. The most common clinical features were as follows: feeding problem was in 19cases, cardiac dysplasia in 20 cases, special appearance in 17 cases, skeletal dysplasia in 15 cases, hypoglycemia in 10 cases and hypotonia in 9 cases. Conclusion: The typical clinical features of KS are not shown in the neonatal period. This disease should be considered when the newborn has feeding problem, abnormal cardiac morphololy, special appearance and other clinical features. Genetic test can help to diagnose earlier in clinical. Early diagnosis can provide accurate information to clinic, may help patients to acquire appropriate treatment and family genetic counseling.