Riant F, Vahedi K, Tournier-Lasserve E
Laboratoire de génétique, groupe hospitalier Lariboisière-Fernand-Widal, AP-HP, 2, rue Ambroise-Paré, 75010 Paris, France.
Rev Neurol (Paris). 2011 May;167(5):401-7. doi: 10.1016/j.neurol.2010.10.016. Epub 2011 Apr 13.
Episodic ataxia (EA) designates a group of autosomal dominant channelopathies that manifest as paroxysmal attacks of imbalance and incoordination. EA conditions are clinically and genetically heterogeneous. Seven types of EA have been reported so far but the majority of clinical cases result from two recognized entities.
Episodic ataxia type 1 (EA1) is characterized by brief episodes of ataxia and dysarthria, and interictal myokymia. Onset occurs during the first two decades of life. Associated epilepsy has been reported in some EA1 patients. EA1 is caused by mutations of the KCNA1 gene coding for the voltage-gated potassium channel Kv1.1. Mutation is mostly missense mutations. Acetazolamide, a carbonic-anhydrase inhibitor, may reduce the frequency and severity of the attacks in some but not all affected individuals. Episodic ataxia type 2 (EA2) is characterized by episodes lasting longer than in EA1, that manifest by ataxia, dysarthria, vertigo, and also, in most of the cases, an interictal nystagmus. Other clinical features as developmental delay or epilepsy can be present in some patients. Brain MRI shows frequently a vermian atrophy. Onset occurs typically in childhood or early adolescence, but can sometimes be in adulthood. EA2 is caused by mutations in CACNA1A, a gene coding for the neuronal voltage-gated calcium channel Cav1.1. For two-thirds of the cases, mutations lead to a stop codon. This type is most often responsive to acetazolamide that reduces the frequency and severity of attacks, but does not appear to prevent the progression of interictal symptoms.
This article summarizes current knowledge on episodic ataxia type 1 and 2 and describes briefly the other types of EA.
Molecular analysis of KCNA1 or CACNA1A provides a confirmation of the diagnosis of EA1 and EA2. Other types remain rare phenotypic variants. Among them, only two genes have been identified: CACNB4 in EA5 and SLC1A3 in EA6 and mutations have been found in a very few cases. No mutation can be detected in some familial cases of episodic ataxia, suggesting further heterogeneity.
发作性共济失调（EA）是一组常染色体显性通道病，表现为阵发性的平衡失调和共济失调。EA病症在临床和遗传方面具有异质性。迄今为止，已报道了七种类型的EA，但大多数临床病例是由两种已知类型引起的。
发作性共济失调1型（EA1）的特征是共济失调和构音障碍的短暂发作，以及发作间期肌纤维颤搐。发病发生在生命的前二十年。一些EA1患者报告有相关癫痫。EA1是由编码电压门控钾通道Kv1.1的KCNA1基因突变引起的。突变大多为错义突变。乙酰唑胺，一种碳酸酐酶抑制剂，可能会降低部分但不是所有受影响个体发作的频率和严重程度。发作性共济失调2型（EA2）的特征是发作持续时间比EA1长，表现为共济失调、构音障碍、眩晕，并且在大多数情况下，发作间期有眼球震颤。一些患者可能出现其他临床特征，如发育迟缓或癫痫。脑部MRI经常显示小脑蚓部萎缩。发病通常发生在儿童期或青春期早期，但有时也可能在成年期。EA2是由CACNA1A基因突变引起的，该基因编码神经元电压门控钙通道Cav1.1。在三分之二的病例中，突变导致终止密码子。这种类型通常对乙酰唑胺有反应，可降低发作的频率和严重程度，但似乎不能阻止发作间期症状的进展。
本文总结了关于发作性共济失调1型和2型的现有知识，并简要描述了其他类型的EA。
对KCNA1或CACNA1A进行分子分析可确诊EA1和EA2。其他类型仍然是罕见的表型变异。其中，仅鉴定出两个基因：EA5中的CACNB4和EA6中的SLC1A3，并且仅在极少数病例中发现了突变。在一些发作性共济失调的家族病例中未检测到突变，提示存在进一步的异质性。
