家族性皮质性肌阵挛震颤伴癫痫，一种神秘的疾病：从表型到病理生理学及遗传学。一项系统综述
Familial Cortical Myoclonic Tremor and Epilepsy, an Enigmatic Disorder: From Phenotypes to Pathophysiology and Genetics. A Systematic Review.
作者信息
van den Ende Tom, Sharifi Sarvi, van der Salm Sandra M A, van Rootselaar Anne-Fleur
机构信息
Department of Neurology and Clinical Neurophysiology, Amsterdam Neuroscience, Academic Medical Center, Amsterdam, The Netherlands.
Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center, Utrecht, The Netherlands.
出版信息
Tremor Other Hyperkinet Mov (N Y). 2018 Jan 23;8:503. doi: 10.7916/D85155WJ. eCollection 2018.
BACKGROUND
Autosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE) is characterized by distal tremulous myoclonus, generalized seizures, and signs of cortical reflex myoclonus. FCMTE has been described in over 100 pedigrees worldwide, under several different names and acronyms. Pathological changes have been located in the cerebellum. This systematic review discusses the clinical spectrum, treatment, pathophysiology, and genetic findings.
METHODS
We carried out a PubMed search, using a combination of the following search terms: cortical tremor, myoclonus, epilepsy, benign course, adult onset, familial, and autosomal dominant; this resulted in a total of 77 studies (761 patients; 126 pedigrees) fulfilling the inclusion and exclusion criteria.
RESULTS
Phenotypic differences across pedigrees exist, possibly related to underlying genetic differences. A "benign" phenotype has been described in several Japanese families and pedigrees linked to 8q (FCMTE1). French patients (5p linkage; FCMTE3) exhibit more severe progression, and in Japanese/Chinese pedigrees (with unknown linkage) anticipation has been suggested. Preferred treatment is with valproate (mind teratogenicity), levetiracetam, and/or clonazepam. Several genes have been identified, which differ in potential pathogenicity.
DISCUSSION
Based on the core features (above), the syndrome can be considered a distinct clinical entity. Clinical features may also include proximal myoclonus and mild progression with aging. Valproate or levetiracetam, with or without clonazepam, reduces symptoms. FCMTE is a heterogeneous disorder, and likely to include a variety of different conditions with mutations of different genes. Distinct phenotypic traits might reflect different genetic mutations. Genes involved in Purkinje cell outgrowth or those encoding for ion channels or neurotransmitters seem good candidate genes.
背景
常染色体显性遗传性家族性皮质肌阵挛性震颤伴癫痫（FCMTE）的特征为远端震颤性肌阵挛、全身性癫痫发作以及皮质反射性肌阵挛体征。FCMTE在全球100多个家系中已有报道，有多个不同的名称和首字母缩写。病理改变定位于小脑。本系统评价讨论了其临床谱、治疗、病理生理学及遗传学发现。
方法
我们在PubMed上进行检索，使用以下检索词组合：皮质震颤、肌阵挛、癫痫、良性病程、成人起病、家族性、常染色体显性；共检索到77项研究（761例患者；126个家系）符合纳入和排除标准。
结果
各系谱存在表型差异，可能与潜在的基因差异有关。在几个与8q相关的日本家族和系谱（FCMTE1）中描述了一种“良性”表型。法国患者（5p连锁；FCMTE3）表现出更严重的病情进展，在日本/中国系谱（连锁情况不明）中提示有遗传早现现象。首选治疗药物为丙戊酸盐（注意致畸性）、左乙拉西坦和/或氯硝西泮。已鉴定出多个基因，其潜在致病性各不相同。
讨论
基于上述核心特征，该综合征可被视为一种独特的临床实体。临床特征还可能包括近端肌阵挛和随年龄增长病情轻度进展。丙戊酸盐或左乙拉西坦，联合或不联合氯硝西泮，可减轻症状。FCMTE是一种异质性疾病，可能包括多种不同的基因发生突变的情况。不同的表型特征可能反映不同的基因突变。参与浦肯野细胞生长的基因或编码离子通道或神经递质的基因似乎是很好的候选基因。
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