Influence of genotype on cardiac phenotype in paediatric hypertrophic cardiomyopathy: a CMR-based study

Abstract Background Paediatric hypertrophic cardiomyopathy (HCM) presents with variable phenotypic expression, influenced by the underlying genetic background. This study aimed to assess genotype-phenotype correlations using cardiac magnetic resonance (CMR) imaging at diagnosis in a cohort of paediatric patients. Methods 126 patients aged ≤18 years with sarcomeric or nonsyndromic familial HCM underwent CMR at diagnosis. Patients were categorized into four groups based on genetic findings: MYBPC3 (n=44), MYH7 (n=47), thin filament variants (TNNT2, TNNI3, or ACTC1) (n=19), and genotype-negative (n=16). Morphological and functional parameters were compared among groups. Results Median age was 12 IQR 10-15 years without significant difference between genotype (p=0.474). Patients with MYH7 mutations were more frequently obstructive compared to other genotypes (p=0.024). There was a trend towards higher prevalence of late gadolinium enhancement (LGE) in patients with thin filament variants and MYH7 (p=0.078). Genotype-negative patients exhibited higher left ventricular ejection fraction (LVEF) and cardiac output (LVCO) compared to other groups (p=0.017 and p=0.048, respectively). Conversely, patients with MYBPC3 mutations had larger indexed left ventricular end-systolic volume (LVESVi) (p=0.022). Conclusion This study highlights distinct CMR-derived phenotypic differences across genetic subgroups in paediatric HCM. MYH7 mutations were associated with a higher prevalence of left ventricular outflow tract obstruction, thin filament variants with increased fibrosis, while genotype-negative patients had higher LVEF. These findings may contribute to improved risk stratification and tailored management in paediatric HCM.