Autosomal recessive desminopathy: an under-recognised disorder

Myofibrillar myopathies (MFMs) are genetically and clinically heterogeneous muscle disorders characterised by sarcoplasmic protein aggregation and myofibrillar disorganisation arising at the Z-disc. Although pathogenic variants are identifiable in ∼50% of cases, and mutations in 16 genes are now recognised to cause MFM, most reported cases follow an autosomal dominant pattern, with autosomal recessive forms considered rare. We describe the clinical, genetic, and pathological features of ten individuals harbouring homozygous variants in DES (desmin). The cohort shows marked clinical variability, with disease onset ranging from infancy to mid-adulthood, with occasional contractures and facial myopathy, whilst cardiac manifestations were surprisingly rare. Muscle pathology was similarly heterogeneous, with most cases lacking hallmark MFM features. These findings demonstrate that autosomal recessive DES mutations generate a broad, distinct clinical spectrum compared with dominant MFM, and that classical MFM histopathology may be absent, potentially contributing to diagnostic delay.