Clinical Characteristics and Genetic Analysis of MYH7-Related Pediatric Cardiomyopathy—A Multicenter Cohort Study

Abstract Objective The clinical phenotypes of MYH7-related pediatric cardiomyopathy are diverse.This study aims to analyze the clinical characteristics, prognosis, and domain-associated genetic characteristics of MYH7-related pediatric cardiomyopathy. Methods This was a multicenter retrospective cohort study. Children with MYH7 gene mutations who first or revisited ten domestic tertiary pediatric cardiovascular hospitals from January 2020 to December 2025 were enrolled. Based on the initial echocardiogram, the patients were divided into three groups: dilation phenotype group, hypertrophy phenotype group, noncompaction cardiomyopathy(NCM) phenotype group. General clinical data, laboratory test, echocardiogram and genetic results were collected from the medical record system. All children were followed up until December 2025, and follow-up echocardiogram results and occurrence of endpoint events were recorded. Log-rank test was used to assess differences in follow-up outcomes among groups. Spearman correlation analysis was used to examine the relationship between clinical phenotype and functional domain, and multiple logistic regression analysis was used to analyze the association between clinical phenotype and genetic functional domain. Results A total of 75 children with MYH7 gene mutations were enrolled, including four families. The median age at first diagnosis was 20.0 (3.0, 80.0) months, with 47 males (62.7%). Based on echocardiogram, there were 34 cases (45.3%) in dilation phenotype group, 16 (21.3%) in hypertrophy phenotype group, and 25 (33.3%) in NCM phenotype group. Significant differences were found among the three groups in age, creatinine, and BNP levels (p < 0.05). A total of 51 mutation sites were identified in the 75 patients, of which 50 were point mutations and one was a deletion mutation (c.2563_2565delGAG). Among the 51 point mutations, nine sites were recurrent. The most frequent recurrent mutation was c.2710C > T (6 cases), followed by c.602T > C, c.1357C > T, c.1106G > A, c.2711G > A, c.2513C > T, c.4498C > T, c.5401G > A, and c.848A > T. Sanger validation was performed in 72 cases. Among them, 21 cases (28.0%) had maternal inherited variants, 19 cases (25.3%) had paternal inherited variants, and 32 cases (42.6%) had de novo variants. Mutation sites in the three phenotype groups were distributed throughout the entire length of the MYH7 gene without significant enrichment in any region. Although mutations in the head region (S1) were more frequent than in the neck region (S2) or tail region (S3), there was no statistically significant difference among the groups (p = 0.369). Spearman correlation analysis showed no correlation between genetic functional domain and clinical phenotype, but a correlation was observed between functional domain and prognosis (p = 0.034, r=-0.281), indicating that mutations in the head region were associated with worse prognosis. Conclusions Children with MYH7 gene mutations exhibit diverse clinical phenotypes with no significant enrichment of mutation sites. In this cohort, no correlation was found between functional domain and clinical phenotype, but mutations located in the head region were associated with poorer prognosis. Molecular-level genetic profiling can offer crucial clues for clinical outcome prediction.