Scheffer Ingrid E, Wallace R H, Phillips F L, Hewson P, Reardon K, Parasivam G, Stromme P, Berkovic S F, Gecz J, Mulley J C
Department of Medicine (Neurology), Epilepsy Research Institute, Austin & Repatriation Medical Centre, University of Melbourne, Neurosciences Building Level 1, Banksia Street, West Heidelberg, Victoria 3081, Australia.
Neurology. 2002 Aug 13;59(3):348-56. doi: 10.1212/wnl.59.3.348.
To describe a new syndrome of X-linked myoclonic epilepsy with generalized spasticity and intellectual disability (XMESID) and identify the gene defect underlying this disorder.
The authors studied a family in which six boys over two generations had intractable seizures using a validated seizure questionnaire, clinical examination, and EEG studies. Previous records and investigations were obtained. Information on seizure disorders was obtained on 271 members of the extended family. Molecular genetic analysis included linkage studies and mutational analysis using a positional candidate gene approach.
All six affected boys had myoclonic seizures and TCS; two had infantile spasms, but only one had hypsarrhythmia. EEG studies show diffuse background slowing with slow generalized spike wave activity. All affected boys had moderate to profound intellectual disability. Hyperreflexia was observed in obligate carrier women. A late-onset progressive spastic ataxia in the matriarch raises the possibility of late clinical manifestations in obligate carriers. The disorder was mapped to Xp11.2-22.2 with a maximum lod score of 1.8. As recently reported, a missense mutation (1058C>T/P353L) was identified within the homeodomain of the novel human Aristaless related homeobox gene (ARX).
XMESID is a rare X-linked recessive myoclonic epilepsy with spasticity and intellectual disability in boys. Hyperreflexia is found in carrier women. XMESID is associated with a missense mutation in ARX. This disorder is allelic with X-linked infantile spasms (ISSX; MIM 308350) where polyalanine tract expansions are the commonly observed molecular defect. Mutations of ARX are associated with a wide range of phenotypes; functional studies in the future may lend insights to the neurobiology of myoclonic seizures and infantile spasms.
描述一种新的伴有全身性痉挛和智力障碍的X连锁肌阵挛癫痫综合征（XMESID），并确定该疾病的基因缺陷。
作者对一个家族进行了研究，该家族中两代内的6名男孩患有难治性癫痫，采用了经过验证的癫痫问卷、临床检查和脑电图研究。获取了既往记录和检查结果。收集了该大家庭271名成员的癫痫疾病信息。分子遗传学分析包括连锁研究和使用定位候选基因方法的突变分析。
所有6名患病男孩均有肌阵挛发作和TCS；2名有婴儿痉挛症，但只有1名有高峰失律。脑电图研究显示弥漫性背景减慢，伴有缓慢的全身性棘波活动。所有患病男孩均有中度至重度智力障碍。在携带者女性中观察到反射亢进。家族中女性家长出现迟发性进行性痉挛性共济失调，提示携带者可能出现晚期临床表现。该疾病定位于Xp11.2 - 22.2，最大对数优势得分为1.8。如最近报道的那样，在新的人类无尾相关同源盒基因（ARX）的同源结构域内鉴定出一个错义突变（1058C>T/P353L）。
XMESID是一种罕见的X连锁隐性肌阵挛癫痫，男孩伴有痉挛和智力障碍。在携带者女性中发现反射亢进。XMESID与ARX中的错义突变相关。该疾病与X连锁婴儿痉挛症（ISSX；MIM 308350）等位，后者常见的分子缺陷是多聚丙氨酸序列扩增。ARX的突变与多种表型相关；未来的功能研究可能有助于深入了解肌阵挛发作和婴儿痉挛症的神经生物学机制。
