Department of Medical and Surgical Sciences, Institute of Neurology, University Magna Graecia, Catanzaro, Italy.
Genetics Department, Hospices Civils de Lyon, Lyon, France.
Epilepsia Open. 2024 Jun;9(3):951-959. doi: 10.1002/epi4.12920. Epub 2024 Mar 27.
Myotonia is a clinical sign typical of a group of skeletal muscle channelopathies, the non-dystrophic myotonias. These disorders are electrophysiologically characterized by altered membrane excitability, due to specific genetic variants in known causative genes (CLCN1 and SCN4A). Juvenile Myoclonic Epilepsy (JME) is an epileptic syndrome identified as idiopathic generalized epilepsy, its genetics is complex and still unclarified. The co-occurrence of these two phenotypes is rare and the causes likely have a genetic background. In this study, we have genetically investigated an Italian family in which co-segregates myotonia, JME, or abnormal EEG without seizures was observed.
All six individuals of the family, 4 affected and 2 unaffected, were clinically evaluated; EMG and EEG examinations were performed. For genetic testing, Exome Sequencing was performed for the six family members and Sanger sequencing was used to confirm the candidate variant.
Four family members, the mother and three siblings, were affected by myotonia. Moreover, EEG recordings revealed interictal generalized sharp-wave discharges in all affected individuals, and two siblings were affected by JME. All four affected members share the same identified variant, c.644 T > C, p.Ile215Thr, in SCN4A gene. Variants that could account for the epileptic phenotype alone, separately from the myotonic one, were not identified.
These results provide supporting evidence that both myotonic and epileptic phenotypes could share a common genetic background, due to variants in SCN4A gene. SCN4A pathogenic variants, already known to be causative of myotonia, likely increase the susceptibility to epilepsy in our family.
This study analyzed all members of an Italian family, in which the mother and three siblings had myotonia and epilepsy. Genetic analysis allowed to identify a variant in the SCN4A gene, which appears to be the cause of both clinical signs in this family.
肌强直是一组骨骼肌通道病（非营养不良性肌强直）的临床特征。这些疾病在电生理上表现为膜兴奋性改变，这是由于已知致病基因（CLCN1 和 SCN4A）的特定遗传变异所致。青少年肌阵挛性癫痫（JME）是一种癫痫综合征，被确定为特发性全面性癫痫，其遗传具有复杂性且尚未阐明。这两种表型的同时出现较为罕见，其原因可能具有遗传背景。在这项研究中，我们对一个意大利家庭进行了基因研究，该家庭中存在肌强直、JME 或无癫痫发作的异常脑电图共分离现象。
对该家庭的 6 名成员（4 名受影响者和 2 名未受影响者）进行了临床评估；进行了肌电图和脑电图检查。对 6 名家庭成员进行了外显子组测序进行基因检测，并使用 Sanger 测序来确认候选变异。
4 名家庭成员（母亲和 3 名兄弟姐妹）患有肌强直。此外，所有受影响的个体的脑电图记录均显示出阵发性全脑棘波放电，其中 2 名兄弟姐妹患有 JME。所有 4 名受影响的成员都携带相同的 SCN4A 基因中的鉴定变异 c.644T>C，p.Ile215Thr。未发现可单独解释癫痫表型而不解释肌强直表型的变异。
这些结果提供了支持性证据，表明肌强直和癫痫表型可能具有共同的遗传背景，这是由于 SCN4A 基因中的变异所致。已知导致肌强直的 SCN4A 致病性变异可能增加了我们家族患癫痫的易感性。
本研究分析了一个意大利家庭的所有成员，该家庭中的母亲和 3 名兄弟姐妹患有肌强直和癫痫。基因分析确定了 SCN4A 基因中的一个变异，该变异似乎是该家庭中这两种临床体征的原因。
