A Distinctive MRI Pattern Resembling Type VI Collagen Myopathy in Novel VWA1-Related Distal Hereditary Motor...

To describe a 51-year-old woman with early-onset weakness and foot deformities carrying a biallelic truncating mutation in the VWA1 gene. The patient underwent laboratory tests, nerve conduction studies with electromyography, muscle magnetic resonance imaging, muscle biopsy, and genetic testing. Neurophysiological studies and biopsy revealed both myopathic and neuropathic features. Muscle magnetic resonance imaging showed a distinctive outside-in pattern of fatty replacement in the vastus lateralis, resembling that seen in type VI collagen-related myopathies. Whole-exome sequencing identified a homozygous pathogenic variant in VWA1, which encodes an extracellular matrix protein found in the basement membranes of nerves and muscles. Recently, truncating mutations in VWA1 have been associated with previously unsolved neuromyopathy cases. In one of these reports, as in the current case, the MRI pattern mimicked that of type VI collagen disorders. Biallelic VWA1 mutations may account for some genetically undiagnosed cases of neuropathy with myopathic features.