In this study, the authors characterized the phenotype of patients with distal myopathy with vocal cord and pharyngeal weakness (VCPDM) due to the p.S85C mutation in the Matrin 3 gene (MATR3, MIM 164015). Recently it has been suggested that patients with this mutation may suffer from familial amyotrophic lateral sclerosis. Sixteen patients from six families with late onset distal myopathy associated with the p.S85C MATR3 mutation were characterized. Patients had a predominantly distal muscle weakness, most severely affecting ankle and wrist dorsiflexion. Relevant proximal and axial weakness was found in six; respiratory impairment in five patients. Dysphagia was diagnosed in six, mild voice abnormalities were found in seven patients. However, laryngoscopy revealed normal vocal cord function. Creatine kinase was normal or mildly elevated. Electromyographically, spontaneous activity was found in 10/14 patients, complex repetitive discharges in 9/14 patients. MRI revealed severe fatty degeneration of distal and upper posterior leg and of paraspinal muscles. Histopathology ranged from mild myopathic to severe dystrophic changes including vacuoles. Absence of sarcomers in the perinuclear region and abnormal invaginations of nuclei were found ultrastructurally. Haplotype analysis showed a common disease specific haplotype of the six families and suggested that these families form a separate cluster. Interpretation. In contrast to the two previously reported families MATR3 related distal myopathy might be associated with relevant axial, proximal, and respiratory muscles weakness but without vocal cord palsy. There were no clinical, electrophysiological, and histopathological signs of lower motor neuron involvement.
