■非营养不良性肌张力障碍是由SCN4A基因中的功能获得突变或CLCN1基因中的功能丧失突变引起的罕见的肌肉过度兴奋障碍。临床上,它们的特点是肌强直,定义为自愿收缩后延迟的肌肉松弛,导致肌肉僵硬的症状,疼痛,疲劳,和弱点。诊断基于病史和检查结果,肌电图上存在肌电强直,和遗传确认。
■在患有临床神经肌肉疾病的患者中进行包括CLCN1和SCN4A基因的下一代测序。肌电图,短期运动测试,体内和体外电生理学,收集定点诱变和异源表达。
■杂合点突变(c.1775C>T,p.Thr592Ile)已在三代以上的五名女性患者中鉴定出肌肉电压门控钠通道α亚基基因(SCN4A),在一个非营养不良性肌强直的家庭中。肌肉僵硬和肌强直主要累及面部和手部,还会影响走路和跑步,出生后早期出现,并表现出明显的冷敏感性。非常热的温度,月经和怀孕也加剧了症状;肌肉疼痛和热身现象是可变的特征。既没有瘫痪性攻击也没有运动后弱点的报道。怀孕期间出现肌肉肥大伴痉挛样疼痛和僵硬增加。使用美西律和乙酰唑胺均可控制症状。肌肉冷却后的短期运动测试揭示了两种不同的模式,具有中等绝对变化的复合肌肉动作电位振幅。
■在该撒丁岛家族中鉴定的SCN4A基因中的p.Thr592Ile突变是肌强直的临床表型的原因。
UNASSIGNED: The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene. Clinically, they are characterized by myotonia, defined as delayed muscle relaxation after voluntary contraction, which leads to symptoms of muscle stiffness, pain, fatigue, and weakness. Diagnosis is based on history and examination findings, the presence of electrical myotonia on electromyography, and genetic confirmation.
UNASSIGNED: Next-generation sequencing including the CLCN1 and SCN4A genes was performed in patients with clinical neuromuscular disorders. Electromyography, Short Exercise Test, in vivo and in vitro electrophysiology, site-directed mutagenesis and heterologous expression were collected.
UNASSIGNED: A heterozygous point mutation (c.1775C > T, p.Thr592Ile) of muscle voltage-gated sodium channel α subunit gene (SCN4A) has been identified in five female patients over three generations, in a family with non-dystrophic myotonia. The muscle stiffness and myotonia involve mainly the face and hands, but also affect walking and running, appearing early after birth and presenting a clear cold sensitivity. Very hot temperatures, menstruation and pregnancy also exacerbate the symptoms; muscle pain and a warm-up phenomenon are variable features. Neither paralytic attacks nor post-exercise weakness has been reported. Muscle hypertrophy with cramp-like pain and increased stiffness developed during pregnancy. The symptoms were controlled with both mexiletine and acetazolamide. The Short Exercise Test after muscle cooling revealed two different patterns, with moderate absolute changes of compound muscle action potential amplitude.
UNASSIGNED: The p.Thr592Ile mutation in the SCN4A gene identified in this Sardinian family was responsible of clinical phenotype of myotonia.