CAUSAL HETEROGENEITY IN ISOLATED LISSENCEPHALY
CAUSAL HETEROGENEITY IN ISOLATED LISSENCEPHALY
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DOI：
10.1212/wnl.42.7.1375
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发表时间：
1992-07-01
期刊：
影响因子：
9.9
通讯作者：
LEDBETTER, DH
中科院分区：
文献类型：
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作者：
DOBYNS, WB;ELIAS, ER;LEDBETTER, DH
我们报告了65例孤立无脑回序列（ILS）患者的临床、细胞遗传学和分子生物学研究。 所有患者均患有不同严重程度的I型无脑回畸形，小脑大体正常。 有些人有额外的大脑异常。 面部外观基本正常。 所有人都有严重到严重的智力迟钝、癫痫发作、肌张力减退演变为痉挛和进食困难。 临床和实验室研究表明病因异质性。 分子研究在44名受试患者中的6名中检测到染色体带17p13.3的微缺失，证实在某些情况下，这一“关键区域”的全部或部分缺失是ILS的原因。 在大多数Miller-Dieker综合征患者中，同一区域有稍大的缺失。 1例患者具有明显平衡的从头相互易位，断点位于Xq 22和2 p25。 来自两个家庭的四个同胞有一个新的，常染色体隐性综合征的ILS新生儿死亡。 临床观察支持的其他原因包括常染色体隐性遗传、宫内感染和宫内灌注衰竭。 那些无法确定病因的ILS先证者有41个同胞，其中3个受累，经验性复发风险为7%。
We report clinical, cytogenetic, and molecular studies in 65 patients with isolated lissencephaly sequence (ILS). All had type I lissencephaly of varying severity and a grossly normal cerebellum. Some had additional brain abnormalities. Facial appearance was essentially normal. All had severe to profound mental retardation, seizures, hypotonia that evolved into spasticity, and feeding difficulties. Clinical and laboratory studies demonstrated etiologic heterogeneity. Molecular studies detected microdeletions in chromosome band 17p13.3 in six of 44 patients tested, confirming that deletion of all or part of this "critical region" is the cause of ILS in some cases. There were slightly larger deletions in the same region in a majority of patients with Miller-Dieker syndrome. One patient had an apparently balanced, de novo reciprocal translocation with breakpoints at Xq22 and 2p25. Four sibs from two families had a new, autosomal recessive syndrome of ILS with neonatal death. Other causes supported by clinical observations include autosomal recessive inheritance, intrauterine infection, and intrauterine perfusion failure. Those ILS probands in whom no etiology could be established had 41 sibs of whom three were affected, giving an empiric recurrence risk of 7%.