Wild Edward J, Tabrizi Sarah J
UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK.
Curr Opin Neurol. 2007 Dec;20(6):681-7. doi: 10.1097/WCO.0b013e3282f12074.
Patients presenting with features of Huntington's disease but lacking the causative genetic expansion can be challenging diagnostically. The differential diagnosis of such Huntington's disease phenocopy syndromes has not recently been reviewed.
Cohort studies have established the relative frequencies of known Huntington's disease phenocopy syndromes, whereas newly described ones have been characterized genetically, clinically, radiologically and pathologically.
About 1% of suspected Huntington's disease cases emerge as phenocopy syndromes. Such syndromes are clinically important in their own right but may also shed light on the pathogenesis of Huntington's disease. Huntington's disease produces a range of clinical phenotypes, and the range of syndromes that may be responsible for Huntington's disease phenocopies is correspondingly wide. Cohort studies have established that, while the majority of phenocopy patients remain undiagnosed, in those patients where a genetic diagnosis is reached the commonest causes are SCA17, Huntington's disease-like syndrome 2 (HDL2), familial prion disease and Friedreich's ataxia. We review the features of the reported genetic causes of Huntington's disease phenocopy syndromes, including HDL1-3, SCA17, familial prion disease, spinocerebellar ataxias, dentatorubral-pallidoluysian atrophy, chorea-acanthocytosis and iron-accumulation disorders. We present an evidence-based framework for the genetic testing of Huntington's disease phenocopy cases.
表现出亨廷顿舞蹈症特征但缺乏致病基因扩增的患者在诊断上具有挑战性。近期尚未对这类亨廷顿舞蹈症表型综合征的鉴别诊断进行综述。
队列研究已确定了已知亨廷顿舞蹈症表型综合征的相对发病率，而新描述的综合征已在基因、临床、放射和病理方面得到了特征描述。
约1%的疑似亨廷顿舞蹈症病例表现为表型综合征。这类综合征本身在临床上就很重要，而且还可能有助于揭示亨廷顿舞蹈症的发病机制。亨廷顿舞蹈症会产生一系列临床表型，可能导致亨廷顿舞蹈症表型的综合征范围相应也很广。队列研究已证实，虽然大多数表型综合征患者仍未得到诊断，但在那些已做出基因诊断的患者中，最常见的病因是SCA17、亨廷顿舞蹈症样综合征2（HDL2）、家族性朊病毒病和弗里德赖希共济失调。我们综述了已报道的亨廷顿舞蹈症表型综合征的遗传病因特征，包括HDL1 - 3、SCA17、家族性朊病毒病、脊髓小脑共济失调、齿状核红核苍白球路易体萎缩症、舞蹈病 - 棘红细胞增多症和铁蓄积障碍。我们为亨廷顿舞蹈症表型病例的基因检测提供了一个基于证据的框架。
