Novel DES mutation presenting with isolated restrictive respiratory failure. Expanding the clinical spectrum

Desminopathies are a clinically heterogeneous group of myopathies, with common histological findings in muscle biopsy. Clinically, they usually present with distal and/or proximal muscle weakness often associated with cardiomyopathy. We present 8 patients from 3 unrelated families manifesting isolated respiratory insufficiency without skeletal muscle weakness or heart disease, because of a mutation in the DES gene.

Clinical and demographic data were acquired from medical records. Muscle MRI studies were performed in 6 patients. A muscle biopsy study was performed in the index case from each family.

Isolated restrictive respiratory dysfunction was observed in all symptomatic patients, with 2 requiring non-invasive ventilation. Three patients were asymptomatic at the time of the study. None of the patients presented skeletal muscle weakness or heart disease, even after 20 years of disease progression. Muscle MRI showed a common pattern with predominant involvement of the semitendinosus muscle. Muscle biopsy showed patches of cytoplasmic inclusions corresponding to desmin aggregates. The genetic study showed heterozygous presence of the p.Arg415Trp mutation in the DES gene in all patients.

We present 5 patients carrying a p.Arg415Trp mutation in the DES gene, manifesting as isolated restrictive respiratory insufficiency without associated skeletal muscle weakness or heart disease. These cases represent a new phenotype associated with DES mutations, thus suggesting that desminopathy should be considered in the diagnostic workup of patients presenting isolated respiratory failure.