Early‐onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND, MIM#604065) is an ultrarare autosomal dominant syndrome related to de novo CACNA1G gain‐of‐function pathogenic variants. All patients with SCA42ND show cerebellar atrophy and/or hypoplasia on neuroimaging and share common features such as dysmorphic features, global developmental delay, and axial hypotonia, all manifesting within the first year of life. To date, only 10 patients with SCA42ND have been reported with functionally confirmed gain‐of‐function variants, bearing either of two recurrent pathogenic variants. We describe a girl with congenital ataxia, without epilepsy, and a de novo p.Ala961Thr pathogenic variant in CACNA1G. We review the published subjects with the aim of better characterizing the dysmorphic features that may be crucial for clinical recognition of SCA42ND. Cerebellar atrophy, together with digital anomalies, particularly broad thumbs and/or halluces, should lead to clinical suspicion of this disease. We describe the first pharmacological attempt to treat a patient with SCA42ND using zonisamide, an antiepileptic drug with T‐type channel blocker activity, in an off‐label indication using an itemized study protocol. No efficacy was observed at the dose tested. However, without pharmacological treatment, she showed a positive evolution in neurodevelopment during the follow‐up.

中文翻译：

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具有神经发育缺陷（SCA42ND）的早期发作的严重脊髓小脑共济失调42：病例报告，药理试验和文献复习

具有神经发育缺陷的早期发作的严重脊髓小脑共济失调42（SCA42ND，MIM＃604065）是与从头开始的CACNA1G功能获得性病原体变异相关的超罕见常染色体显性综合征。所有患有SCA42ND的患者在影像学检查中均显示小脑萎缩和/或发育不全，并具有共同的特征，例如畸形特征，整体发育迟缓和轴向性肌张力低下，均在生命的第一年内表现出来。迄今为止，仅报道了10例SCA42ND患者具有功能确诊的功能获得型变异体，带有两个复发性致病变异体之一。我们描述先天性共济失调一个女孩，无癫痫，以及从头p.Ala961Thr致病变种在CACNA1G。我们复习已发表的主题，目的是更好地表征可能对SCA42ND的临床识别至关重要的畸形特征。小脑萎缩以及数字异常，尤其是拇指和/或幻觉异常，应导致对该疾病的临床怀疑。我们使用逐项研究方案在非标签适应症中描述了使用zonisamide（具有T型通道阻滞剂活性的抗癫痫药）治疗SCA42ND患者的首次药理尝试。在所测试的剂量下未观察到功效。但是，在没有药物治疗的情况下，她在随访过程中显示出神经发育的积极进展。