Dystonia-plus syndromes
Dystonia-plus syndromes
复制标题
DOI：
10.1111/j.1468-1331.2010.03049.x
复制
发表时间：
2010-07-01
影响因子：
5.1
通讯作者：
Gasser, T.
中科院分区：
文献类型：
--
作者：
Asmus, F.;Gasser, T.
肌张力障碍综合征代表了一组不同的疾病，其中肌张力障碍伴有其他神经特征，可以频繁地检测到基因突变。有症状的肌张力障碍和以肌张力障碍为临床表现的复杂神经退行性疾病被排除在这一类别之外。目前，以下疾病被归类为肌张力障碍综合征：多巴反应性肌张力障碍(DRD)是一种主要发生于儿童的神经代谢障碍，具有两种不同的遗传模式：常染色体显性形式的GTP-环水解酶I(GCH1，DYT5)杂合突变导致DRD外显性降低，对左旋多巴有良好和持久的反应。常染色体隐性遗传型DRD是由酪氨酸羟基酶(TH)或七叶蝶呤还原酶(SPR)基因纯合或复合杂合突变引起的。在AR-DRD中，表型通常更严重，包括认知障碍和发育迟缓。脑脊液蝶呤代谢产物分析可确诊。或者，全面的基因检测在高达80%的患者中产生致病突变。肌阵挛肌张力障碍(M-D)是由肌聚糖基因(SGCE)杂合性突变引起的。肌张力障碍一般只是轻微到中度的，像闪电一样的肌阵挛很少在休息时发生，可以由复杂的运动任务触发，比如写作和画图。这两个特征，加上发病年龄在25岁以下，强烈预测M-D中的SGCE突变，并将这种遗传病与其他‘干’型肌张力障碍区分开来。肌张力障碍和帕金森综合症的组合只有在非退行性综合征中很少观察到。除DRD外，还对另外两种综合征进行了分类。快速起病的肌张力障碍-帕金森综合征(RPD，DYT12)是一种罕见的疾病，症状突然发作几分钟到几天，突出的球受累和帕金森综合症，对左旋多巴缺乏反应。这种罕见表型的患者应该筛查Na+/K+ATPaseα3亚单位(ATP1A3)基因的突变，即使没有家族史也是如此。最近，一种新的肌张力障碍-帕金森综合症(DYT16)被发现与PRKRA基因突变有关，其与基底节疾病的关系尚不清楚
Dystonia-plus syndromes represent a heterogeneous group of diseases, where dystonia is accompanied by other neurological features and gene mutations can be detected frequently. Symptomatic dystonias and complex neurodegenerative diseases with dystonia as part of the clinical presentation are excluded from this category. At present, the following disorders are categorized as dystonia-plus syndromes: Dopa-responsive dystonia (DRD) is a mostly pediatric-onset, neurometabolic disorder with two different modes of inheritance: in its autosomal-dominant form, heterozygous mutations of GTP-cyclohydrolase I (GCH1, DYT5) cause DRD with reduced penetrance and excellent and lasting response to levodopa. Autosomal-recessive (AR) forms of DRD are caused by homozygous or compound heterozygous mutations of the tyrosine hydroxylase (TH) or the sepiapterin reductase (SPR) gene. In AR-DRD, the phenotype is generally more severe including cognitive deficits and developmental delay. Diagnosis can be confirmed by analysis of CSF pterine metabolites. Alternatively, comprehensive genetic testing yields causative mutations in up to 80% of patients. Myoclonus-dystonia (M-D) is caused by heterozygous mutations of the epsilon-sarcoglycan gene (SGCE). Dystonia is generally only mild to moderate, and 'lightning-like' myoclonic jerks occur rarely at rest and can be triggered by complex motor tasks like writing and drawing. Both features together with an age at onset below 25 years strongly predict SGCE mutation in M-D and differentiate this genetic disease from other 'jerky' dystonias. The combination of dystonia and parkinsonism can only be rarely observed in non-degenerative syndromes. Besides DRD, two additional syndromes have been classified. Rapid-onset dystonia-parkinsonism (RPD, DYT12) is a rare disorder with an abrupt onset of symptoms over minutes to days, prominent bulbar involvement and parkinsonism with a lack of response to levodopa. Patients with this rare phenotype should be screened for mutation in the Na+/K+ ATPase alpha3-subunit (ATP1A3) gene, even if family history is negative. Recently, a novel form of dystonia-parkinsonism (DYT16) has been found to be linked to mutations in the PRKRA gene, whose relation to basal ganglia disorders is yet unknown