[One novel pathologic variation in KMT2D cause Kabuki syndrome with hearing loss as the main phenotype and related research on types of deafness].

Objective:To make the molecular diagnosis of a patient complaining hearing loss and with specific facial features, developmental delay, vertebral dysplasia, hypotonia and other suspected phenotypes of Kabuki make-up syndrome（KS）; to investigate the characteristics and main phenotypes of KS. Method:①Whole-exome sequencing and bioinformatics analysis were performed for proband and her parents. ②Literatures describing the clinical features of KS patients with clear molecular diagnosis from the period of Aug 2010 to Mar 2019 were collected from databases of PubMed and CNKI. Result:①The proband carries the c. 15777insT variant（p. Pro5260fs*10） in KMT2D gene. The variant causes the termination codon to appear prematurely. KMT2D c. 15777insT was classified as PVS1+PS1+PM2 according to the ACMG variation interpretation standard, which is a disease-causing mutation. The c. 15777insT was first reported as a pathogenic mutation of KS. ②77 peer-reviewed publications on KS were analysed including 462 patients with KS. The main findings were intellectual disability（305 cases）, congenital heart defects（227 cases）, hypotonia（184 cases）, short fingers（147 cases）, short stature（144 cases）, cleft palate（139 cases）, hearing loss（101 cases） and developmental delay（99 cases）. Of the 101 patients with hearing loss, 11 were confirmed to have conductive hearing loss（1 with recurrent otitis media）, 3 with mixed hearing loss, 12 with sensorineural deafness（1 with recurrence otitis media） and 75 patients with unidentified types of deafness（28 with recurrent otitis media）. Conclusion:KS involves defects of a wide range of organs, with each organ showing different severity of symptoms, which is easily misdiagnosed from the phenotypes. We suggest the diagnosis on hearing loss in KS patients should be strengthened. KMT2D and KDM6A are two pathogenic genes that have been identified for KS. With the increase of age, its typical clinical phenotypes become more and more obvious. When there is only atypical suspected KS symptoms in the early neonatal period, relevant genetic test should be performed as soon as possible to achieve early diagnosis and intervention.