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Cohort studyJournal of the American College of Cardiology · 2026

Sex and Age Specific Genetic Risk Across the Dilated and Arrhythmogenic Cardiomyopathy Spectrum: Insights From the SHaRe Registry.

Sophie L V M Stroeks, Nicole K Bart, Joseph Rossano … DCM/ACM SHaRe Investigators

PediatricsCohort study

DSP variants are more common in females with dilated or arrhythmogenic cardiomyopathy.

Sex and Age Specific Genetic Risk Across the Dilated and Arrhythmogenic Cardiomyopathy Spectrum: Insights From the SHaRe Registry.

Sophie L V M Stroeks et al. · Journal of the American College of Cardiology · 2026

Background

Dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM) are progressive cardiac muscle disorders with phenotypic and genetic overlap.

Purpose

The aim of this study was to define sex-based differences in genetic architecture and age at diagnosis of DCM/ACM across pediatric and adult populations.

Methods

Genetically tested adult and pediatric DCM/ACM patients and asymptomatic genotype-positive relatives enrolled in the multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed.

n = 3,410 patients

Results

DSP variants are more common in females with dilated or arrhythmogenic cardiomyopathy

OR by subgroup · 95% CI

More results

Among 3,410 patients, a 61% male predominance was present across subgroups of genotype positive, genotype negative, and variants of uncertain significance (P = 0.008), with significant gene-specific variation.

More results

Age at diagnosis was comparable between sexes, except in TTNtv carriers, among whom males exhibited earlier disease onset compared with females (median age 45 years [Q1-Q3: 33-55 years] vs 51 years [Q1-Q3: 38-60 years]; P = 0.003).

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Conclusion · 1 of 3

Gene-specific sex differences influence disease prevalence and age at onset in DCM/ACM. TTNtv are more common with earlier onset in males, whereas DSP and non-TTN sarcomeric variants predominate in females.

Conclusion · 2 of 3

Pediatric-onset DCM/ACM is genetically distinct and caused predominantly by non-TTN sarcomeric variants, especially during infancy.

Conclusion · 3 of 3

These findings support age- and sex-informed surveillance strategies and prioritize future research into the mechanisms of observed sex-based differences.

Post

Sex and Age Specific Genetic Risk Across the Dilated and Arrhythmogenic Cardiomyopathy Spectrum: Insights From the SHaRe Registry.

DSP variants are more common in females with dilated or arrhythmogenic cardiomyopathy.

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