Key result
Homozygous DES p.R415W mutation linked to early-onset mixed RCM-HCM and life-threatening arrhythmia in a pediatric patient.
Why the study?
Restrictive cardiomyopathy is rare and typically caused by autosomal dominant or de novo mutations; autosomal recessive inheritance and desmin mutations are less characterized.
Case Report (n=1)
No
This case report identifies a novel homozygous missense variant in the DES gene causing early-onset restrictive cardiomyopathy and life-threatening arrhythmia in a child, expanding knowledge of desmin-related cardiomyopathy.
May prompt DES testing in early-onset mixed pediatric cardiomyopathy; extends desminopathy spectrum but leaves open broader validation.
Restrictive cardiomyopathy (RCM) is a rare cardiac disease characterized by the predominance of severe diastolic dysfunction, normal or mildly increased ventricular wall thickness, and either normal or mildly reduced ejection fraction. All known RCM genes are localized on autosomes. In most cases, the mutations are inherited in an autosomal dominant mode or appear as de novo mutations. The present report describes a case with early-onset RCM and life-threatening arrhythmia, which was inherited in an autosomal recessive manner. The child developed ventricular arrhythmia at one month of age, and a mixed phenotype dominated by restrictive cardiomyopathy with coexistent hypertrophic cardiomyopathy (RCM - HCM) at one year of age. and required hospitalization for anti - heart failure treatment due to heart failure at three years of age. The patient suffered from ventricular fibrillation and cardiac arrest at four years of age, which was rescued by extracorporeal membrane oxygenation and subsequent heart transplantation. Whole genome sequencing of the proband revealed a novel homozygous missense variant (NM_001927.3: c.1243 C > T [p.R415W]) in the Desmin (DES) gene, which was inherited from heterozygous unaffected parents. This case further expands our knowledge of desmin-related cardiomyopathy in children.
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Wang et al. (2025) conducted a case report in Restrictive cardiomyopathy with hypertrophic cardiomyopathy (RCM-HCM) (n=1). Homozygous DES gene mutation (p.R415W) was evaluated on Development of RCM-HCM and life-threatening arrhythmia. A homozygous p.R415W mutation in the DES gene caused early-onset severe mixed restrictive and hypertrophic cardiomyopathy with life-threatening arrhythmia in a pediatric patient.
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