Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Mov Disord. 2022 Jan;37(1):16-24. doi: 10.1002/mds.28823. Epub 2021 Oct 12.
Huntington disease is an autosomal dominant inherited brain disorder that typically becomes manifest in adulthood. Juvenile-onset Huntington disease refers to approximately 5% of patients with symptom onset before the age of 21 years. The causal factor is a pathologically expanded CAG repeat in the Huntingtin gene. Age at onset is inversely correlated with CAG repeat length. Juvenile-onset patients have distinct symptoms and signs with more severe pathology of involved brain structures in comparison with disease onset in adulthood. The aim of this review is to compare clinical and pathological features in juvenile- and adult-onset Huntington disease and to explore which processes potentially contribute to the observed differences. A specific focus is placed on molecular mechanisms of mutant huntingtin in early neurodevelopment and the interaction of a neurodegenerative disease and postnatal brain maturation. The importance of a better understanding of pathophysiological differences between juvenile- and adult-onset Huntington disease lies in development and implementation of new therapeutic strategies. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
亨廷顿病是一种常染色体显性遗传的脑疾病，通常在成年期表现出来。青少年发病的亨廷顿病是指大约 5%的患者在 21 岁之前出现症状。致病因素是亨廷顿基因中病理性扩张的 CAG 重复。发病年龄与 CAG 重复长度呈负相关。与成年发病相比，青少年发病的患者具有明显不同的症状和体征，受累脑结构的病理学更严重。本综述旨在比较青少年和成年发病的亨廷顿病的临床和病理特征，并探讨哪些过程可能导致观察到的差异。特别关注突变亨廷顿蛋白在早期神经发育中的分子机制以及神经退行性疾病与出生后大脑成熟的相互作用。更好地了解青少年和成年发病的亨廷顿病之间的病理生理差异的重要性在于开发和实施新的治疗策略。© 2021 作者。运动障碍由 Wiley 期刊有限责任公司代表国际帕金森病和运动障碍协会出版。
