DES Gene Risk Stratification (Myofibrillar Myopathy) Calculator

DES Gene Risk Stratification (proposed, literature-informed): Explanation and Clinical Context This calculator implements a pragmatic, composite risk tool for individuals with DES gene variants (desmin-related myofibrillar myopathy) that combines genotype (pathogenic/likely pathogenic vs VUS/negative), presence of clinical cardiomyopathy, left ventricular ejection fraction (LVEF), arrhythmic burden (non-sustained VT, sustained VT/ventricular fibrillation), conduction disease, family history of sudden cardiac death (first-degree relative), and unexplained syncope. Each element is weighted to reflect its relative association with adverse cardiac outcomes in reported cohorts of DES mutation carriers and expert consensus for genetic cardiomyopathies. The score is intentionally conservative and designed as a clinical decision aid rather than a definitive rule: "Low risk" suggests routine surveillance with cardiac imaging and rhythm monitoring, "Intermediate risk" recommends enhanced surveillance and consideration of longer rhythm monitoring, "High risk" indicates consideration of primary prevention implantable cardioverter-defibrillator (ICD) in the presence of additional adverse features, and "Very high risk" supports strong consideration for ICD and specialized tertiary management.

This model is offered because, as of the cited literature, there is no universally validated numeric DES-specific risk score; clinicians should interpret this output in the context of detailed phenotype, family history, cardiac MRI findings (fibrosis), ambulatory monitoring results, and shared decision-making with the patient and genetic counselors.