Brenner David, Baumgartner Tobias, von Spiczak Sarah, Lewerenz Jan, Weis Roger, Grimmer Anja, Gaspirova Petra, Wurster Claudia D, Kunz Wolfram S, Wagner Jan, Minassian Berge A, Elger Christian E, Ludolph Albert C, Biskup Saskia, Döcker Dennis
Department of Neurology, University of Ulm, Ulm, Germany.
Department of Epileptology, University of Bonn Hospital, Bonn, Germany.
Neurol Res Pract. 2019;1. doi: 10.1186/s42466-019-0040-2. Epub 2019 Nov 12.
Lafora progressive myoclonus epilepsy (Lafora disease) is a rare, usually childhood-onset, fatal neurodegenerative disease caused by biallelic mutations in (Laforin) or (, Malin). The epidemiology of Lafora disease in Germany is largely unknown. The objective of this retrospective case series is to characterize the genotypes and phenotypes of patients with Lafora disease living in Germany.
The patients described in this case series initially had the suspected clinical diagnosis of Lafora disease, or unclassified progressive myoclonus epilepsy. Molecular genetic diagnostics including next generation sequencing-based diagnostic panel analysis or whole exome sequencing was performed.
The parents of four out of the 11 patients are nonconsanguineous and of German origin while the other patients had consanguineous parents. Various variants were found in (six patients) and in (five patients). Eight variants have not been reported in the literature so far. The patients bearing novel variants had typical disease onset during adolescence and show classical disease courses.
This is the first larger case series of Lafora patients in Germany. Our data enable an approximation of the prevalence of manifest Lafora disease in Germany to 1,69 per 10 million people. Broader application of gene panel or whole-exome diagnostics helps clarifying unclassified progressive myoclonus epilepsy and establish an early diagnosis, which will be even more important as causal therapy approaches have been developed and are soon to be tested in a phase I study.
拉福拉进行性肌阵挛癫痫（拉福拉病）是一种罕见的、通常在儿童期发病的致命性神经退行性疾病，由EPM2A（拉福林）或EPM2B（NHLRC1，马啉）的双等位基因突变引起。拉福拉病在德国的流行病学情况 largely unknown。本回顾性病例系列的目的是描述居住在德国的拉福拉病患者的基因型和表型。
本病例系列中描述的患者最初临床疑似诊断为拉福拉病或未分类的进行性肌阵挛癫痫。进行了分子遗传学诊断，包括基于下一代测序的诊断 panel 分析或全外显子组测序。
11名患者中有4名患者的父母是非近亲且为德国血统，而其他患者的父母是近亲。在EPM2A（6名患者）和EPM2B（5名患者）中发现了各种变异。到目前为止，文献中尚未报道8种变异。携带新变异的患者在青春期有典型的疾病发作，并表现出经典的病程。
这是德国首个较大规模的拉福拉病患者病例系列。我们的数据使德国显性拉福拉病的患病率估计约为每1000万人中有1.69例。更广泛地应用基因 panel 或全外显子组诊断有助于明确未分类的进行性肌阵挛癫痫并建立早期诊断，随着病因治疗方法的开发并即将在I期研究中进行测试，这将变得更加重要。
