Department of Neurodegenerative Disease, Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
Eur J Neurol. 2010 Jul;17 Suppl 1:37-45. doi: 10.1111/j.1468-1331.2010.03049.x.
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 .
肌张力障碍综合征代表一组异质性疾病，其中肌张力障碍伴有其他神经特征，并且经常可以检测到基因突变。该类别排除了症状性肌张力障碍和以肌张力障碍为临床表现一部分的复杂神经退行性疾病。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）是一种主要在儿童期发病的神经代谢疾病，具有两种不同的遗传方式：在常染色体显性遗传形式中，GTP-环水解酶 I（GCH1，DYT5）的杂合突变导致 DRD，其外显率降低，对左旋多巴有极好且持久的反应。DRD 的常染色体隐性（AR）形式是由酪氨酸羟化酶（TH）或蝶呤还原酶（SPR）基因的纯合或复合杂合突变引起的。在 AR-DRD 中，表型通常更严重，包括认知缺陷和发育迟缓。通过 CSF 蝶呤代谢物分析可确诊。或者，全面的基因检测可在高达 80%的患者中产生致病突变。肌阵挛性肌张力障碍（M-D）是由ε-肌聚糖基因（SGCE）的杂合突变引起的。肌张力障碍通常仅为轻度至中度，“闪电样”肌阵挛性抽搐很少在休息时发生，并且可以由复杂的运动任务如书写和绘画触发。发病年龄低于 25 岁，加上肌阵挛和肌张力障碍，强烈预测 M-D 中的 SGCE 突变，并将这种遗传性疾病与其他“抽搐性”肌张力障碍区分开来。非退行性综合征中只能很少观察到肌张力障碍和帕金森病的组合。除了 DRD，还有两种综合征被分类。快速进展性肌张力障碍-帕金森病（RPD，DYT12）是一种罕见疾病，其症状在数分钟至数天内突然出现，明显球部受累和帕金森病，对左旋多巴无反应。即使家族史阴性，也应筛查这种罕见表型患者的 Na(+)/K(+) ATPase alpha3-亚基（ATP1A3）基因突变。最近，发现一种新型的肌张力障碍-帕金森病（DYT16）与 PRKRA 基因突变有关，但其与基底节疾病的关系尚不清楚。
