Child Neurology and Psychiatry Unit, Department of Pediatrics, Presidio Ospedaliero Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy.
Human Neurosciences Department, Sapienza University of Rome, 00185 Rome, Italy.
Int J Mol Sci. 2023 Feb 14;24(4):3796. doi: 10.3390/ijms24043796.
Genetic early-onset Parkinsonism is unique due to frequent co-occurrence of hyperkinetic movement disorder(s) (MD), or additional neurological of systemic findings, including epilepsy in up to 10-15% of cases. Based on both the classification of Parkinsonism in children proposed by Leuzzi and coworkers and the 2017 ILAE epilepsies classification, we performed a literature review in PubMed. A few discrete presentations can be identified: Parkinsonism as a late manifestation of complex neurodevelopmental disorders, characterized by developmental and epileptic encephalopathies (DE-EE), with multiple, refractory seizure types and severely abnormal EEG characteristics, with or without preceding hyperkinetic MD; Parkinsonism in the context of syndromic conditions with unspecific reduced seizure threshold in infancy and childhood; neurodegenerative conditions with brain iron accumulation, in which childhood DE-EE is followed by neurodegeneration; and finally, monogenic juvenile Parkinsonism, in which a subset of patients with intellectual disability or developmental delay (ID/DD) develop hypokinetic MD between 10 and 30 years of age, following unspecific, usually well-controlled, childhood epilepsy. This emerging group of genetic conditions leading to epilepsy or DE-EE in childhood followed by juvenile Parkinsonism highlights the need for careful long-term follow-up, especially in the context of ID/DD, in order to readily identify individuals at increased risk of later Parkinsonism.
遗传性早发性帕金森病具有独特性，因为其常伴有运动障碍（MD）或其他神经系统或全身性表现，包括癫痫，在多达 10-15%的病例中发生。基于 Leuzzi 及其同事提出的儿童帕金森病分类和 2017 年 ILAE 癫痫分类，我们在 PubMed 上进行了文献回顾。可以确定几种离散的表现形式：帕金森病作为复杂神经发育障碍的晚期表现，其特征为发育性和癫痫性脑病（DE-EE），具有多种难治性癫痫发作类型和严重异常的脑电图特征，伴有或不伴有先前的多动性 MD；在伴有婴儿期和儿童期癫痫发作阈值降低的综合征性疾病背景下出现帕金森病；具有脑铁积累的神经退行性疾病，其中儿童期 DE-EE 后出现神经退行性变；最后是单基因性青少年帕金森病，其中一部分伴有智力障碍或发育迟缓（ID/DD）的患者在 10 至 30 岁之间出现运动障碍，且通常为非特异性、得到良好控制的儿童期癫痫。这组新出现的遗传性疾病导致儿童期癫痫或 DE-EE 后出现青少年帕金森病，突出表明需要进行仔细的长期随访，尤其是在 ID/DD 背景下，以便及时识别具有更高帕金森病风险的个体。
