Congenital Heart diseases (CHDs) are one of the most frequent congenital anomalies and represent a significant source of morbidity and mortality in infants. The underlying causes of CHDs are still not well understood, though it has long been hypothesized to involve both genetic and environmental contributions. Variants in MYH6 have emerged as potential genetic contributors to congenital heart disease (CHDs), though genotype-phenotype correlations remain incompletely described. The aim is to provide a detailed description of cardiac phenotypes in patients with CHDs and carriers of MYH6 variants, in a French cohort.

We included patients with CHDs in whom genetic testing identified relevant MYH6 variants ascertained through a collaborative network of French genetics laboratories. Clinical data, follow up and familial data were retrospectively collected from medical records. All cardiac lesions were included, and each patient had defined a principal phenotype.

We included 28 patients, from whom 67.9% had left heart diseases as principal phenotype notably hypoplastic left heart syndrome (39.3%), left heart obstructions at mutiples sites (17.9%), and coarctation of aorta (10.7%) (Fig. 1). One third of patients had other CHDs such as tetralogy of Fallot, pulmonary stenosis and septal defects. An unexpected high prevalence (35.7%) of persistent left superior caval vein (LSCV) was found compared to literature reports (0.2–5%), raising its potential as a clinical marker for MYH6 variants. The 19 variants were most of time first described, heterozygous, missenses and inherited for 60.7% of the cohort. Family screening demonstrated incomplete penetrance and variable phenotypic expressivity.

Our findings support broad indications of molecular testing for MYH6 in left heart diseases and other CHDs particularly when familial recurrence is uncertain. LSCV could represent a clinical indicator associated with MYH6 carriers.