The Myocardial Accumulation of Aggregated Desmin Protein in a Case of Desminopathy with a de novo DES p.R406W Mutation

Desminopathy is a cardiac and skeletal myopathy caused by disease-causing variants in the desmin (DES) gene and represents a subgroup of myofibrillar myopathies, where cytoplasmic desmin-postive immunoreactivity is the pathological hallmark. We herein report a 28-year-old Japanese man who was initially diagnosed with sporadic hypertrophic cardiomyopathy with atrioventricular block at 9 years old and developed weakness in the soft palate and extremities. The myocardial tissue dissected during implantation of the ventricularassisted device showed a dilated phase of hypertrophic cardiomyopathy and intracellular accumulation of proteinase K-resistant desmin aggregates. Genetic testing confirmed a de novo mutation of DES, which has already been linked to desminopathy. As the molecular diagnosis of desminopathy is challenging, particularly if patients show predominantly cardiac signs and a routine skeletal muscle biopsy is unavailable, these characteristic pathological findings of endomyocardial proteinase K-resistant desmin aggregates might aid in clinical practice.

Automated summary

Desminopathy is a cardiac and skeletal myopathy caused by disease-causing variants in the DES gene. In this report, we describe a 28-year-old Japanese patient who was initially diagnosed with sporadic hypertrophic cardiomyopathy with atrioventricular block and developed weakness in the soft palate and extremities. Genetic testing confirmed a de novo mutation of the DES gene. The challenging molecular diagnosis of desminopathy makes the pathological findings of endomyocardial proteinase K-resistant desmin aggregates helpful in clinical practice.