Case Report: Exploring KMT2D mutation in Shone syndrome

Introduction Shone syndrome is a rare congenital heart disease characterized by multilevel left-sided obstructive lesions. KMT2D variants cause Kabuki syndrome and are frequently associated with left-sided obstructive congenital heart defects, but their contribution to Shone syndrome remains uncertain. Methods We report a 4-year-old girl with a Shone syndrome phenotype. Trio whole-exome sequencing (WES) was performed in the proband and her parents, with Sanger sequencing for confirmation and segregation analysis. Echocardiography and CT angiography were used to delineate cardiac anatomy. Results Imaging and intraoperative findings demonstrated a supramitral ring with mitral stenosis, abnormal subvalvular apparatus, an interrupted/hypoplastic aortic arch with extensive collateral circulation, and a bicuspid aortic valve. Trio-WES identified a heterozygous KMT2D variant (NM_003482.4:c.15565G > A, p.Gly5189Arg) in the proband, which was also present in her clinically unaffected mother and younger sister, indicating maternal inheritance with variable expressivity. Conclusions This report describes a child with multilevel left-sided obstruction and an inherited KMT2D variant, together with limited Kabuki-like facial features that did not meet the 2019 international consensus clinical criteria for Kabuki syndrome. While the observation raises the possibility that KMT2D-related pathways may contribute to Shone complex, a causal relationship cannot be inferred from a single family and requires additional genetic and functional studies.