Matrin3 myopathy: Distal and axial myopathy with pathology of the nucleus and the perinuclear region

Introduction: Recently it was shown, that a mutation in the MATR3 gene causes vocal cord and pharyngeal weakness with distal myopathy (VCPDM) in a North American and in a Bulgarian pedigree. MATR3 encodes Matrin 3, a component of the nuclear matrix. Vocal cord or swallowing dysfunction occurred in most cases of VCPDM. Detailed clinical descriptions or structural data of muscles were not given. Here we report on the clinical and myopathological data of the worldwide third family in detail. In four individuals of our German family (III3, IV2, IV3, V2, see pedigree. *: index patient, D: Diabetes mellitus) the same S85C mutation in the MATR3 gene was detected. Three of them were symptomatic (III3, IV2, IV3).

Results: Age of onset (years) was 45 in III3, 25 in IV2, and 38 in IV3. There was no significant difference between the reported families and our patients. In patients IV2 and IV3, myalgias were the initial symptom. Patients III3 and IV2 had distal and proximal weakness of the lower limbs and showed the Gowers manoeuvre. Patient IV3 had mild proximal weakness of the legs and generalized myalgia. Patients III3 and IV2 had a nearly total fatty degeneration of the following muscles on MRI: anterior tibial, peroneus longus and brevis, gastrocnemius, soleus, semimembranosus, semitendinosus, paraspinal and deltoid. Involvement of the posterior compartment of the thigh and of the paraspinal muscles was not reported so far. Patient IV3 and the asymptomatic patient V2 showed a degeneration of the medial part of the gastrocnemius muscle on MRI. None of the patients had vocal cord palsy. Diabetes mellitus type II cosegregated with the myopathy. Creatine kinase ranged from normal to 5-fold elevation. Heart involvement was not found in all patients by MRI, ultrasound, and Holter-ECG. Muscle biopsy revealed myopathic/dystrophic changes. Abnormal invaginations of the nucleus, perinuclear absence of sarcomers, and vacuoles were found on electron microscopy.

Conclusion: The S85C missense mutation in the MATR3 gene can be associated with a predominantly distal and axial myopathy but also with proximal weakness. Vocal cord palsy is not obligatory. Myalgias and degeneration of the medial gastrocnemius muscle can be the first sign. Paraspinal and posterior thigh muscles are significantly affected on MRI. Heart muscle is not involved. We suggest an association of Diabetes mellitus type II and the MATR3 mutation in the pedigree presented here.