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.