Huntington disease
Huntington disease
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DOI：
10.1002/0470018860.s00410
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发表时间：
2010-01
期刊：
影响因子：
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通讯作者：
Joseph Jankovic;Mark Hallett;Michael S. Okun;Cynthia L. Comella;Stanley Fahn;Jennifer Goldman
中科院分区：
文献类型：
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作者：
Joseph Jankovic;Mark Hallett;Michael S. Okun;Cynthia L. Comella;Stanley Fahn;Jennifer Goldman
亨廷顿舞蹈病（HD）是由4号染色体短臂上的三核苷酸重复（胞嘧啶、腺嘌呤和鸟嘌呤[CAG]）扩增引起的常染色体显性神经变性疾病。运动诊断的平均年龄为39岁，诊断时的年龄与CAG突变的长度相关。HD的前驱症状可以在运动诊断前15年被识别，其特征在于情感识别、气味识别、处理速度、时间估计和生产以及精神异常方面的细微损伤。HD显示基底神经节中的中等多刺神经元特别脆弱。进行性脑功能障碍和神经元死亡导致34年来运动、认知和行为控制功能的隐性丧失（前驱期17年，诊断后17年）。治疗计划依赖于遗传咨询，必要时的精神症状治疗，物理治疗和环境改造。有两种治疗方法可以减少舞蹈病，但没有疾病修饰疗法。然而，实验性疗法正在迅速出现，具有多种和各种靶点，并且目前正在进行沉默突变HD基因的基因疗法。本章回顾了HD的临床和神经病理学描述，并讨论了潜在的潜在机制和动物模型，用于表征和跟踪疾病的诊断和临床评估，治疗计划和研究的挑战，以促进护理。
Huntington disease (HD) is a autosomal dominant neurodegenerative disease caused by expansion of a trinucleotide repeat (cytosine, adenine, and guanine [CAG]) on the short arm of chromosome four. Average age of motor diagnosis is 39 years, and age at diagnosis is associated with the length of the CAG mutation. The prodrome of HD can be recognized 15 years prior to motor diagnosis and is characterized by subtle impairments in emotional recognition, smell identification, speed of processing, time estimation and production, and psychiatric abnormalities. HD shows particular vulnerability of the medium spiny neuron in the basal ganglia. Progressive brain dysfunction and neuron death lead to insidious loss of function in motor, cognitive, and behavioral control over 34 years (17 prodromal and 17 post-diagnosis). Treatment plans rely on genetic counseling, psychiatric symptom treatment as needed, physical therapy, and environmental modifications. There are two treatments for the reduction of chorea, but there are no disease-modifying therapies. Experimental therapeutics are rapidly emerging with multiple and various targets, however, and gene therapies to silence the mutant HD gene are currently ongoing. This chapter reviews clinical and neuropathological descriptions of HD and discusses potential underlying mechanisms and animal models, diagnostic and clinical assessments used to characterize and track the disease, treatment planning, and challenges for research to advance care.