CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene
CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene
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DOI：
10.1212/wnl.0b013e3181ffe4bb
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发表时间：
2010-11-30
期刊：
影响因子：
9.9
通讯作者：
Bird, T.
中科院分区：
文献类型：
--
作者：
Chen, D. -H.;Sul, Y.;Bird, T.
背景：最近有报道在2C型Charcot-Marie-Tooth(CMT2C)伴声带麻痹患者中发现瞬时受体电位阳离子通道V亚家族成员4基因(TRPV4)突变。同一基因的其他突变已经在不同的骨骼发育不良家系中被描述。方法：我们对2个CMT2C家系的TRPV4基因进行了临床评估、电生理学和遗传分析。结果：两个多世代家系的运动性轴索神经病与变异性声带麻痹相关。声带麻痹从无到严重不等，2名患者需要永久气管切开。一个患有轻度神经病的家庭也表现出明显的矮小，比美国白人的平均身高低2个SD以上。有一个例子是多发性头部畸形。在该家系中发现了一个新的TRPV4基因S542Y突变。另一个家族有更严重的进行性运动神经病，伴有感觉丧失，但不太明显的身材矮小和TRPV4的R315W突变。结论：CMT2C伴轴突神经病、声带麻痹、身材矮小是一种独特的综合征，与TRPV4基因突变有关。TRPV4的突变可导致骨骼、周围神经或两者的异常，并可能导致高度不同的骨科和神经学表型。神经病学(R)2010；75：1968-1975
Background: Recently, mutations in the transient receptor potential cation channel, subfamily V, member 4 gene (TRPV4) have been reported in Charcot-Marie-Tooth Type 2C (CMT2C) with vocal cord paresis. Other mutations in this same gene have been described in separate families with various skeletal dysplasias. Further clarification is needed of the different phenotypes associated with this gene.Methods: We performed clinical evaluation, electrophysiology, and genetic analysis of the TRPV4 gene in 2 families with CMT2C.Results: Two multigenerational families had a motor greater than sensory axonal neuropathy associated with variable vocal cord paresis. The vocal cord paresis varied from absent to severe, requiring permanent tracheotomy in 2 subjects. One family with mild neuropathy also manifested pronounced short stature, more than 2 SD below the average height for white Americans. There was one instance of dolichocephaly. A novel S542Y mutation in the TRPV4 gene was identified in this family. The other family had a more severe, progressive, motor neuropathy with sensory loss, but less remarkable short stature and an R315W mutation in TRPV4. Third cranial nerve involvement and sleep apnea occurred in one subject in each family.Conclusion: CMT2C with axonal neuropathy, vocal cord paresis, and short stature is a unique syndrome associated with mutations in the TRPV4 gene. Mutations in TRPV4 can cause abnormalities in bone, peripheral nerve, or both and may result in highly variable orthopedic and neurologic phenotypes. Neurology (R) 2010;75:1968-1975