Article

Centronuclear myopathies (CNM) are rare inherited disorders
characterized by nuclei placed in rows in the central part of the muscle fibres.
Three CNM-causing genes have been identified, with MTM1 mutations provoking
X-linked myotubular myopathy, DNM2 mutations provoking autosomal dominant (AD)
CNM, and BIN1 mutations provoking autosomal recessive (AR) CNM. METHODS: In this
retrospective monocentric study, we describe 14 adult patients (age>18 years)
diagnosed with CNM in our hospital in the 2000-2012 interval. Twelve patients
originated from four families, and two patients presented with sporadic CNM. All
patients underwent standardized clinical examinations, biological tests,
electrophysiological studies, muscle biopsy, and molecular testing. RESULTS:
Seven patients developed CNM before age 15, and seven after age 25. All patients
presented with distal upper and lower limbs weakness, and normal CK levels.
Disease severity remained mild, with all patients being able to walk without
assistance even after decades-long disease duration. Cognitive impairment was
found in seven cases, axonal polyneuropathy in six cases and ophthalmoparesis and
ptosis in five cases. DNM2 gene mutations were found in eight patients, whereas
BIN1 and MTM1 mutations were not observed. Overall, no molecular diagnosis was
available for six patients. CONCLUSION: Adult CNM is a slowly progressive distal
myopathy with normal CK levels sometimes associated with cognitive impairment,
axonal polyneuropathy, and ophthalmoparesis and ptosis. DNM2 mutations were found
in eight patients, including AD and sporadic cases, and represent the major cause
of CNM in this adult cohort. In contrast, no MTM1 and BIN1 mutations were
observed in our series, leaving six patients with no molecular diagnosis. As
these six patients presented with AD (3 cases), AR (2 cases), and sporadic (1
case) CNM, it is likely that several CNM-causing genes remain to be discovered.
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Langue : ANGLAIS