From the Department of Neurology (J.v.d.A., A.S., A.M., P.S., B.D.) and Center for Medical Genetics (B.D.), Ghent University Hospital, Belgium; Institute for Inherited Metabolic Disorders (I.J., A.P., H.H., S.K.), Prague, First Faculty of Medicine, Charles University in Prague, Czech Republic; Neurodegenerative Brain Diseases Group (A.S., S.V.M., C.V.B.), Center for Molecular Neurology, VIB; Neuropathology and Laboratory of Neurochemistry and Behavior (A.S.), Laboratory of Neurogenetics (S.V.M., C.V.B.), and Laboratory of Neuromuscular Pathology and Translational Neurosciences (C.C.-d.G.), Institute Born-Bunge, University of Antwerp, Belgium; Institute of Pathology, First Faculty of Medicine (H.H., R.M.), Charles University and General University Hospital; Department of Pathology and Molecular Medicine (R.M.), National Reference Laboratory for Diagnostics of Human Prion Diseases, Thomayer Hospital, Prague, Czech Republic; Epilepsy Research Centre, Department of Medicine (S.F.B.), University of Melbourne, Austin Health, Heidelberg, Australia; and Inserm U1167 (B.D.), Laboratoire d'Excellence Distalz, Institut Pasteur de Lille, Longevity Research Center, Université de Lille, France. J.v.d.A. is currently affiliated with the Department of Clinical Neurosciences and WT/CRUK Gurdon Institute, University of Cambridge, UK.
Neurology. 2018 Feb 20;90(8):e658-e663. doi: 10.1212/WNL.0000000000004999. Epub 2018 Jan 19.
The progressive myoclonic epilepsies (PME) are a heterogeneous group of disorders in which a specific diagnosis cannot be made in a subset of patients, despite exhaustive investigation. repeat expansions are emerging as an important causal factor in several adult-onset neurodegenerative disorders, in particular frontotemporal lobar degeneration and amyotrophic lateral sclerosis. An association with PME has not been reported previously.
To identify the causative mutation in a Belgian family where the proband had genetically unexplained PME.
We report a 33-year old woman who had epilepsy since the age of 15 and then developed progressive cognitive deterioration and multifocal myoclonus at the age of 18. The family history suggested autosomal dominant inheritance of psychiatric disorders, epilepsy, and dementia. Thorough workup for PME including whole exome sequencing did not reveal an underlying cause, but a repeat expansion was found in our patient and affected relatives. Brain biopsy confirmed the presence of characteristic p62-positive neuronal cytoplasmic inclusions.
mutation analysis should be considered in patients with PME and psychiatric disorders or dementia, even when the onset is in late childhood or adolescence.
进行性肌阵挛性癫痫（PME）是一组异质性疾病，尽管进行了详尽的检查，但仍有一部分患者无法明确诊断。重复扩展作为几种成人发病的神经退行性疾病（特别是额颞叶变性和肌萎缩性侧索硬化症）的一个重要病因因素已经显现。之前尚未有报道称其与 PME 有关。
鉴定一名基因上无法解释的 PME 先证者的比利时家族中的致病突变。
我们报告了一名 33 岁的女性，她在 15 岁时就患有癫痫，随后在 18 岁时出现进行性认知功能恶化和多灶性肌阵挛。家族史提示存在常染色体显性遗传的精神障碍、癫痫和痴呆。尽管对 PME 进行了全面的检查，包括全外显子组测序，但并未发现潜在病因，然而我们的患者和受影响的亲属存在 重复扩展。脑部活检证实存在特征性 p62 阳性神经元胞质内包涵体。
即使发病在儿童晚期或青春期，对于 PME 伴有精神障碍或痴呆的患者，也应考虑进行突变分析。
