CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is poorly documented. We studied 18 patients (10 males) carrying de novo or inherited CACNA1A mutations, with median age of 2,5 years at epilepsy onset. Eight mutations were novel. Two variants known leading to gain of function (GOF) were found in 5 patients. Five other patients had non-sense variants leading to loss of function (LOF). Seizures were most often revealed by either status epilepticus (SE) (n = 8), eventually triggered by fever (n = 5), or absences/behavioural arrests (n = 7). Non-epileptic paroxysmal events were frequent and consisted in recurrent hemiplegic accesses (n = 9), jitteriness in the neonatal period (n = 6), and ocular paroxysmal events (n = 9). Most of the patients had early permanent cerebellar dysfunction (n = 16) and early moderate to severe global developmental delay (GDD)/intellectual deficiency (ID) (n = 17). MRI was often abnormal, with cerebellar (n = 8) and/or cerebral (n = 6) atrophy. Stroke-like occurred in 2 cases. Some antiepileptic drugs including topiramate, levetiracetam, lamotrigine and valproate were effective on seizures. Acetazolamide and calcium channel blockers were often effective when used. More than half of the patients had refractory epilepsy. CACNA1A mutation should be evoked in front of 2 main electro-clinical phenotypes that are associated with permanent cerebellar dysfunction and moderate to severe GDD/ID. The first one, found in all 5 patients with GOF variants, is characterized by intractable seizures, early and recurrent SE and hemiplegic accesses. The second, less severe, found in 5 patients with LOF variants, is characterized by refractory early onset absence seizures.

CACNA1A致病突变涉及各种神经表型，包括发作性共济失调 (EA2)、脊髓小脑共济失调 (SCA6) 和家族性偏瘫偏头痛 (FHM1)。癫痫病的记录很少。我们研究了 18 名携带新发或遗传性CACNA1A 的患者（10 名男性）突变，癫痫发作时的中位年龄为 2.5 岁。八个突变是新的。在 5 名患者中发现了两种已知导致功能获得 (GOF) 的变异。其他五名患者具有导致功能丧失（LOF）的无意义变异。癫痫发作最常由癫痫持续状态 (SE) (n = 8) 显示，最终由发烧 (n = 5) 或缺席/行为停止 (n = 7) 触发。非癫痫发作性事件频繁发生，包括复发性偏瘫（n = 9）、新生儿期的抖动（n = 6）和眼阵发性事件（n = 9）。大多数患者有早期永久性小脑功能障碍（n = 16）和早期中度至重度全面发育迟缓（GDD）/智力缺陷（ID）（n = 17）。MRI 常常异常，伴有小脑 (n = 8) 和/或脑 (n = 6) 萎缩。2例发生卒中样。一些抗癫痫药物包括托吡酯、左乙拉西坦、拉莫三嗪和丙戊酸盐对癫痫发作有效。使用乙酰唑胺和钙通道阻滞剂通常有效。超过一半的患者患有难治性癫痫。CACNA1A突变应在与永久性小脑功能障碍和中度至重度 GDD/ID 相关的 2 种主要电临床表型之前诱发。第一个在所有 5 名 GOF 变异患者中发现，其特征是难治性癫痫发作、早期和复发性 SE 以及偏瘫通路。第二个不太严重，在 5 名 LOF 变异患者中发现，其特征是难治性早发性失神发作。