X-Linked lissencephaly with abnormal genitalia as a tangential migration disorder causing intractable epilepsy: Proposal for a new term, "interneuronopathy"
X-Linked lissencephaly with abnormal genitalia as a tangential migration disorder causing intractable epilepsy: Proposal for a new term, "interneuronopathy"
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DOI：
10.1177/08830738050200042001
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发表时间：
2005-04-01
影响因子：
1.9
通讯作者：
Dobyns, WB
中科院分区：
文献类型：
--
作者：
Kato, M;Dobyns, WB
带有异常生殖器的x连锁无脑畸形是第一个人类疾病，其中大脑切向迁移缺陷已被证明。伴有生殖器异常的x连锁无脑畸形男性患者表现为顽固性癫痫发作，特别是从出生第一天开始出现阵挛性惊厥或肌阵挛，但迄今脑电图未见婴儿痉挛或心律失常。脑磁共振成像显示前部厚脑回和后部无脑回伴轻度皮质厚，胼胝体发育不全，基底节区发育不良。ARX是一种具有4个聚丙氨酸序列的配对类同源盒基因，是导致x连锁无脑畸形的主要基因。Arx基因敲除小鼠脑内γ-氨基丁酸（GABA）能神经元切向迁移和分化异常。在人类x连锁无脑畸形与异常生殖器，一项神经病理学研究表明，中间神经元的损失。同时，ARX的聚丙氨酸扩增可引起症状性或非症状性韦斯特综合征和非症状性智力迟钝。与ARX突变相关的x连锁无脑畸形伴异常生殖器和韦斯特综合征的惊人致痫性被认为是由涉及切向迁移障碍的中间神经元紊乱引起的。我们建议用“间神经病变”来形容这种情况。
X-linked lissencephaly with abnormal genitalia is the first human disorder in which deficient tangential migration in the brain has been demonstrated. Male patients with X-linked lissencephaly with abnormal genitalia show intractable seizures, especially clonic convulsions or myoclonus from the first day of life, but neither infantile spasms nor hypsarrhythmia on electroencephalograms so far. Brain magnetic resonance imaging shows anterior pachygyria and posterior agyria with a mildly thick cortex, agenesis of the corpus callosum, and dysplastic basal ganglia. ARX, a paired-class homeobox gene with four polyalanine sequences, is a responsible gene for X-linked lissencephaly with abnormal genitalia. The brain of Arx knockout mice shows aberrant tangential migration and differentiation of γ-aminobutyric acid (GABA)ergic interneurons. In human X-linked lissencephaly with abnormal genitalia, a neuropathologic study has suggested a loss of interneurons. Meanwhile, polyalanine expansion of ARX causes symptomatic or nonsymptomatic West's syndrome and nonsyndromic mental retardation. The striking epileptogenicity of X-linked lissencephaly with abnormal genitalia and West's syndrome associated with ARX mutations is considered to be caused by a disorder of interneurons involving a tangential migration disorder. We propose "interneuronopathy" as a term for this.