Illuminating the Genetic Basis of Congenital Heart Disease in Patients with Kabuki Syndrome

TL;DR

This study identifies the most common heart defects in Taiwanese patients with Kabuki syndrome caused by KMT2D mutations.

Contribution

The study provides a detailed characterization of CHD types in Asian Kabuki syndrome patients with KMT2D mutations.

Findings

73.9% of patients with KMT2D variants had congenital heart defects.

Left-sided obstructive lesions and septal defects were the most common CHD types.

No clear genotype–phenotype correlations were found in the studied population.

Abstract

Congenital heart defects (CHDs) affect a substantial proportion of patients with Kabuki syndrome. However, the prevalence and type of CHD and the genotype–phenotype correlations in Asian populations are not fully elucidated. This study performed a retrospective analysis of 23 Taiwanese patients with molecularly confirmed Kabuki syndrome. Twenty-two patients presented with pathogenic variants in the KMT2D gene. Comprehensive clinical assessments were performed. A literature review was conducted to summarize the spectrum of CHDs in patients with Kabuki syndrome. In total, 16 (73.9%) of 22 patients with pathogenic KMT2D variants had CHDs. The most common types of CHD were atrial septal defects (37.5%), ventricular septal defects (18.8%), coarctation of the aorta (18.8%), bicuspid aortic valve (12.5%), persistent left superior vena cava (12.5%), mitral valve prolapse (12.5%), mitral regurgitation (12.5%), and patent ductus arteriosus (12.5%). Other cardiac abnormalities were less common. Further, there were no clear genotype–phenotype correlations found. A literature review revealed similar patterns of CHDs, with a predominance of left-sided obstructive lesions and septal defects. In conclusion, the most common types of CHDs in Taiwanese patients with Kabuki syndrome who presented with KMT2D mutations are left-sided obstructive lesions and septal defects.

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