Genetic and Phenotypic Spectrum of KMT2D Variants in Taiwanese Case Series of Kabuki Syndrome

Abstract

Kabuki syndrome (KS) is a rare genetic disorder characterized by distinct facial features, intellectual disability, and multiple congenital anomalies. We conducted a comprehensive analysis of the genetic and phenotypic spectrum of KS in a Taiwanese patient group of 23 patients. KMT2D variants were found in 22 individuals, with missense (26.1%), nonsense (21.7%), and frameshift (17.4%) variants being the most prevalent. One patient had a KMT2D variant of uncertain significance. The most common clinical characteristics included distinct facial features (100%), intellectual disability (100%), developmental delay (95.7%), speech delay (78.3%), hypotonia (69.6%), congenital heart abnormalities (69.6%), and recurrent infections (65.2%). Other abnormalities included hearing loss (39.1%), seizures (26.1%), cleft palate (26.1%), and renal anomalies (21.7%). This study broadens the mutational and phenotypic spectrum of KS in the Taiwanese population, highlighting the importance of comprehensive genetic testing and multidisciplinary clinical evaluations for diagnosis and treatment.

Keywords: KMT2D; Kabuki syndrome; Taiwan; phenotypic heterogeneity.

Figure 1

(a) The prevalence of KMT2D variants (16 variants) in Taiwanese patients with Kabuki syndrome. The bar graph illustrates the distribution of KMT2D variants in the study patient group. (b) Distribution of the pathogenicity classifications of KMT2D variants (16 variants) identified in the Taiwanese patient group. The pie chart illustrates the number of variants classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS). (c) Distribution of the different types of KMT2D variants (16 variants) identified in the Taiwanese patient group. The pie chart illustrates the proportion of missense, nonsense, frameshift, in-frame deletion, splicing, and gross deletion variants.