Département de Neurologie, hôpital de Hautepierre, hôpitaux universitaires, 1, avenue Molière, 67098 Strasbourg, France; Inserm U692, faculté de médecine, université de Strasbourg, 8(e) étage, bâtiment 3, 11, rue Humann, 67085 Strasbourg cedex, France.
Rev Neurol (Paris). 2013 Aug-Sep;169(8-9):625-31. doi: 10.1016/j.neurol.2012.12.006. Epub 2013 Aug 9.
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.
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.
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.
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.
核纤层肌病（CNM）是一种罕见的遗传性疾病，其特征是肌肉纤维中央部分的核排成一行。已经确定了三个导致 CNM 的基因，MTM1 突变引起 X 连锁肌小管肌病，DNM2 突变引起常染色体显性（AD）CNM，而 BIN1 突变引起常染色体隐性（AR）CNM。
在这项回顾性的单中心研究中，我们描述了 2000-2012 年间在我院诊断为 CNM 的 14 例成年患者。12 例患者来自四个家系，2 例患者表现为散发性 CNM。所有患者均接受了标准化的临床检查、生物学检查、电生理学研究、肌肉活检和分子检测。
7 例患者在 15 岁前发病，7 例在 25 岁后发病。所有患者均表现为远端上下肢无力，且 CK 水平正常。疾病严重程度仍较轻，所有患者即使在疾病持续数十年后仍能在没有帮助的情况下行走。7 例患者出现认知障碍，6 例患者出现轴索性多发性神经病，5 例患者出现眼肌麻痹和上睑下垂。8 例患者发现 DNM2 基因突变，而未发现 BIN1 和 MTM1 基因突变。总体而言，6 例患者未进行分子诊断。
成人 CNM 是一种进展缓慢的远端肌病，CK 水平正常，有时伴有认知障碍、轴索性多发性神经病和眼肌麻痹和上睑下垂。在这组成年患者中，发现了 8 例 DNM2 基因突变，包括 AD 和散发性病例，这是 CNM 的主要原因。相反，在我们的研究中未观察到 MTM1 和 BIN1 基因突变，导致 6 例患者无法进行分子诊断。由于这 6 例患者分别表现为 AD（3 例）、AR（2 例）和散发性（1 例）CNM，很可能还有其他几个导致 CNM 的基因有待发现。
