PDF(Pubmed)
Abstract：
Non-dystrophic myotonias (NDM) encompass chloride and sodium channelopathy. Mutations in CLCN1 lead to either the autosomal dominant form or the recessive form of myotonia congenita (MC). The main symptom is stiffness worsening after rest and improving by physical exercise. Patients with recessive mutations often show muscle hypertrophy, and transient weakness mostly in their lower limbs. Mutations in SCN4A can lead to Hyper-, Hypo- or Normo-kalemic Periodic Paralysis or to different forms of myotonia (Paramyotonia Congenita-PMC and Sodium Channel Myotonia-SCM and severe neonatal episodic laryngospasm-SNEL). SCM often presents facial muscle stiffness, cold sensitivity, and muscle pain, whereas myotonia worsens in PMC patients with the repetition of the muscle activity and cold. Patients affected by chloride or sodium channelopathies may show similar phenotypes and symptoms, making the diagnosis more difficult to reach. Herein we present a woman in whom sodium and chloride channelopathies coexist yielding a complex phenotype with features typical of both MC and PMC. Disease onset was in the second decade with asthenia, weakness, warm up and limb stiffness, and her symptoms had been worsening through the years leading to frequent heavy retrosternal compression, tachycardia, stiffness, and symmetrical pain in her lower limbs. She presented severe lid lag myotonia, a hypertrophic appearance at four limbs and myotonic discharges at EMG. Her symptoms have been triggered by exposure to cold and her daily life was impaired. All together, clinical signs and instrumental data led to the hypothesis of PMC and to the administration of mexiletine, then replaced by acetazolamide because of gastrointestinal side effects. Analysis of SCN4A revealed a new variant, p.Glu1607del. Nonetheless the severity of myotonia in the lower limbs and her general stiffness led to hypothesize that the impairment of sodium channel, Nav1.4, alone could not satisfactorily explain the phenotype and a second genetic \"factor\" was hypothesized. CLCN1 was targeted, and p.Met485Val was detected in homozygosity. This case highlights that proper identification of signs and symptoms by an expert neurologist is crucial to target a successful genetic diagnosis and appropriate therapy.
摘要：
非营养不良性肌痛（NDM）包括氯化物和钠通道病。CLCN1中的突变导致先天性肌强直(MC)的常染色体显性形式或隐性形式。主要症状是休息后僵硬恶化，通过体育锻炼改善。隐性突变患者常表现为肌肉肥大,和短暂的无力大多在他们的下肢。SCN4A的突变可以导致Hyper-，低血或常血钾周期性麻痹或不同形式的肌强直（先天性肌强直-PMC和钠通道肌强直-SCM和严重的新生儿发作性喉痉挛-SNEL）。SCM经常表现出面部肌肉僵硬，冷灵敏度,肌肉疼痛,而PMC患者的肌强直随着肌肉活动和寒冷的重复而恶化。受氯化物或钠通道病影响的患者可能表现出相似的表型和症状，使诊断变得更加困难。在此，我们介绍了一个女性，其中钠和氯通道病共存，产生具有MC和PMC典型特征的复杂表型。疾病的发作是在第二个十年，伴有虚弱，弱点,热身和肢体僵硬，多年来，她的症状一直在恶化，导致频繁的严重胸骨后压迫，心动过速,刚度,下肢对称疼痛。她表现出严重的眼睑滞后肌强直，四肢肥厚外观和肌电图肌强直放电。她的症状是由于暴露于寒冷而引起的，她的日常生活受到损害。一起,临床体征和仪器数据导致了PMC的假设和美西律的给药，然后用乙酰唑胺代替，因为胃肠道副作用。对SCN4A的分析揭示了一个新的变体，p.Glu1607del.尽管如此，下肢肌强直的严重程度和她的全身僵硬导致假设钠通道受损，仅靠Nav1.4无法令人满意地解释表型，并假设了第二个遗传“因子”。CLCN1是目标,和p.Met485Val检测纯合性。这种情况突出表明，由神经科专家正确识别体征和症状对于成功的基因诊断和适当的治疗至关重要。
