BACKGROUND CACNA1A-related disorders present with persistent progressive and non-progressive cerebellar ataxia and paroxysmal events: epileptic seizures and non-epileptic attacks. These phenotypes overlap and co-exist in the majority of patients. OBJECTIVE To describe phenotypes in infantile onset CACNA1A-related disorder and to explore intra-familial variations and genotype-phenotype correlations. MATERIAL AND METHODS This study was a multicenter international collaboration. A retrospective chart review of CACNA1A patients was performed. Clinical, radiological, and genetic data were collected and analyzed in 47 patients with infantile-onset disorder. RESULTS Paroxysmal non-epileptic events (PNEE) were observed in 68% of infants, with paroxysmal tonic upward gaze (PTU) noticed in 47% of infants. Congenital cerebellar ataxia (CCA) was diagnosed in 51% of patients including four patients with developmental delay and only one neurological sign. PNEEs were found in 63% of patients at follow-up, with episodic ataxia (EA) in 40% of the sample. Cerebellar ataxia was found in 58% of the patients at follow-up. Four patients had epilepsy in infancy and nine in childhood. Seven infants had febrile convulsions, three of which developed epilepsy later; all three patients had CCA. Cognitive difficulties were demonstrated in 70% of the children. Cerebellar atrophy was found in only one infant but was depicted in 64% of MRIs after age two. CONCLUSIONS Nearly all of the infants had CCA, PNEE or both. Cognitive difficulties were frequent and appeared to be associated with CCA. Epilepsy was more frequent after age two. Febrile convulsions in association with CCA may indicate risk of epilepsy in later childhood. Brain MRI was normal in infancy. There were no genotype-phenotype correlations found.

中文翻译：

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婴儿型 CACNA1A 相关疾病的临床表型

背景 CACNA1A 相关疾病表现为持续进行性和非进行性小脑共济失调和阵发性事件：癫痫发作和非癫痫发作。这些表型在大多数患者中重叠并共存。目的 描述婴儿型 CACNA1A 相关疾病的表型，并探讨家族内变异和基因型-表型相关性。材料和方法 本研究是一项多中心的国际合作。对 CACNA1A 患者进行了回顾性图表审查。收集和分析了 47 名婴儿期疾病患者的临床、放射学和遗传数据。结果 在 68% 的婴儿中观察到阵发性非癫痫事件 (PNEE)，在 47% 的婴儿中观察到阵发性强直向上凝视 (PTU)。51% 的患者被诊断为先天性小脑性共济失调 (CCA)，其中包括 4 名发育迟缓和仅 1 名神经系统体征的患者。随访时 63% 的患者发现 PNEE，40% 的样本中出现发作性共济失调 (EA)。58% 的患者在随访中发现小脑性共济失调。4 名患者在婴儿期患有癫痫，9 名在儿童期患有癫痫。7 名婴儿出现高热惊厥，其中 3 名后来发展为癫痫；三名患者均患有 CCA。70% 的儿童表现出认知困难。仅在一名婴儿中发现小脑萎缩，但在 64% 的 2 岁以后的 MRI 中发现了小脑萎缩。结论 几乎所有婴儿都患有 CCA、PNEE 或两者都有。认知困难很常见，似乎与 CCA 相关。两岁以后癫痫发病率更高。与 CCA 相关的热性惊厥可能表明在儿童后期有癫痫风险。婴儿时期脑部 MRI 正常。没有发现基因型-表型相关性。