METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
CONCLUSIONS: 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.
方法:家庭中的所有六个人,4个受影响,2个不受影响,进行临床评估;进行肌电图和脑电图检查。基因检测,对六个家族成员进行外显子组测序,并使用Sanger测序来确认候选变体。
结果:四个家庭成员,母亲和三个兄弟姐妹,受到肌强直的影响。此外,脑电图记录显示所有受影响的个体发生间期广泛性锐波放电,和两个兄弟姐妹受到JME的影响。所有四个受影响的成员共享相同的识别变体,c.644T>C,p.Ile215Thr,SCN4A基因。可以单独解释癫痫表型的变体,与肌强直性的分开,未被识别。
结论:这些结果提供了支持证据,表明强直性和癫痫表型可能具有共同的遗传背景,由于SCN4A基因的变异。SCN4A致病性变异,已经知道是肌强直的原因,可能会增加我们家庭对癫痫的易感性。
结论:这项研究分析了意大利家庭的所有成员,其中母亲和三个兄弟姐妹患有肌强直和癫痫。遗传分析允许鉴定SCN4A基因中的变体,这似乎是这个家族中两种临床症状的原因。