Siskind Carly, Feely Shawna M E, Bernes Saunder, Shy Michael E, Garbern James Y
Department of Neurology, Wayne State University, Detroit, MI 48201, USA.
J Neurol Sci. 2009 Apr 15;279(1-2):109-13. doi: 10.1016/j.jns.2008.12.031. Epub 2009 Feb 3.
X-linked Charcot Marie Tooth disease (CMT1X) is a hereditary demyelinating neuropathy caused by mutations in the GJB1 gene encoding the gap junction protein connexin 32 (Cx32). Some GJB1 mutations have been reported to cause transient clinical CNS dysfunction. We report a boy with persistent CNS abnormalities possibly caused by CMT1X.
A five year old boy was evaluated by clinical, electrophysiological, MRI and genetic testing.
The patient's early motor milestones were normal to age 5 months. His subsequent course was one of slow improvement punctuated by brief periods of loss of ability to sit between age 5 and 10 months, loss of language between 12 months and 2 years and 1 episode of non-clinically observed resolved left-sided facial weakness. At age 5, he had truncal instability, appendicular ataxia, and dysarthric speech. Cognition was normal. He had mild toe weakness and intrinsic muscle atrophy. MRI evaluation was abnormal. Electrophysiologic testing revealed slowed motor conduction velocities and sensory responses of low amplitude. Genetic workup was normal excepting a novel missense mutation in GJB1, causing a p.54N>H substitution.
The patient has persistent CNS abnormalities characterized by dysarthria and ataxia. These are similar to transient CNS abnormalities reported in patients with CMT1X. These CNS findings may be the direct result of his novel Cx32 mutation.
X连锁型夏科-马里-图思病（CMT1X）是一种遗传性脱髓鞘性神经病变，由编码缝隙连接蛋白连接蛋白32（Cx32）的GJB1基因突变引起。据报道，一些GJB1突变会导致短暂的临床中枢神经系统功能障碍。我们报告一名可能由CMT1X引起的持续性中枢神经系统异常的男孩。
对一名5岁男孩进行了临床、电生理、磁共振成像和基因检测。
患者5个月龄前运动发育里程碑正常。随后其病情呈缓慢改善过程，期间有短暂波动，5至10个月龄时出现短暂坐立能力丧失，12个月至2岁时出现语言能力丧失，还有1次左侧面部无力发作但未临床观察到恢复过程。5岁时，他有躯干不稳、肢体共济失调和构音障碍。认知功能正常。他有轻度足趾无力和固有肌萎缩。磁共振成像评估结果异常。电生理检查显示运动传导速度减慢和感觉反应波幅降低。除了GJB1基因存在一个导致p.54N>H替换的新错义突变外，基因检查结果正常。
该患者存在以构音障碍和共济失调为特征的持续性中枢神经系统异常。这些与CMT1X患者中报道的短暂性中枢神经系统异常相似。这些中枢神经系统表现可能是其新的Cx32突变的直接结果。
