CONGENITAL MYOPATHIES – CENTRONUCLEAR MYOPATHIES: EP.27 CPEO-like presentation of X-linked myotubular myopathy in an adult male

Abstract

A 42-year-old male presented with the complaint of acute onset double vision in our emergency room. Examination revealed a tall stature, impaired eye movements in all directions, in particular upwards and left side abduction, the latter likely the cause of the acute complaints, and mild symmetrical ptosis compensated by permanent frontalis muscle contraction. As no evidence for myasthenic variability was found and CK was elevated 300 – 550 U/l (ULN 190), vastus lateralis muscle biopsy was performed under suspicion of atypical chronic progressive external ophthalmoplegia (CPEO). Some atrophic and hypertrophic fibres as well as nuclear clumps were attributed to a sensorimotor neuropathy. Few cytochrome c oxidase-negative fibres and internalised myonuclei were seen as signs of mitochondrial myopathy. However, genetic diagnostics failed to detect a mitochondrial cause of CPEO. Instead, we found the previously undescribed hemizygous variant c.1038G>C (p.Trp346Cys)in MTM1, raising the possibility of an unusually mild manifestation of X-linked myotubular myopathy (XLMTM). Western blot confirmed low MTM1 expression in skeletal muscle. Upon repeated history taking, one of the patient's brothers was found to be treated for similar ophthalomogical findings while his other brother, two daughters and his parents are reported to be free of any neuromuscular symptoms. Ophthalmoplegia and ptosis are known to be common in all phenotypes associated with MTM1 mutations. However, most males with the disease are affected severely at birth, many with life-threatening respiratory insufficiency, and only milder phenotypes reach ambulation and independent breathing at all. Even the majority of manifesting female carriers show muscle weakness exceeding what we observed in more than 10 years follow-up in our patient who does not show any skeletal muscle weakness to date.