Michelucci Roberto, Pulitano Patrizia, Di Bonaventura Carlo, Binelli Simona, Luisi Concetta, Pasini Elena, Striano Salvatore, Striano Pasquale, Coppola Giangennaro, La Neve Angela, Giallonardo Anna Teresa, Mecarelli Oriano, Serioli Elena, Dazzo Emanuela, Fanciulli Manuela, Nobile Carlo
IRCCS - Institute of Neurological Sciences of Bologna, Unit of Neurology, Bellaria Hospital, Bologna, Italy.
Department of Neurology and Psychiatry, University of Rome "Sapienza", Policlinico Umberto 1° Hospital, Roma, Italy.
Epilepsy Behav. 2017 Mar;68:103-107. doi: 10.1016/j.yebeh.2016.12.003. Epub 2017 Jan 28.
To describe the clinical phenotype of 7 families with Autosomal Dominant Lateral Temporal Lobe Epilepsy (ADLTE) related to Reelin (RELN) mutations comparing the data with those observed in 12 LGI1-mutated pedigrees belonging to our series.
Out of 40 Italian families with ADLTE, collected by epileptologists participating in a collaborative study of the Commission for Genetics of the Italian League against Epilepsy encompassing a 14-year period (2000-2014), 7 (17.5%) were found to harbor heterozygous RELN mutations. The whole series also included 12 (30%) LGI1 mutated families and 21 (52.5%) non-mutated pedigrees. The clinical, neurophysiological, and neuroradiological findings of RELN and LGI1 mutated families were analyzed.
Out of 28 affected individuals belonging to 7 RELN mutated families, 24 had sufficient clinical data available for the study. In these patients, the epilepsy onset occurred at a mean age of 20years, with focal seizures characterized by auditory auras in about 71% of the cases, associated in one-third of patients with aphasia, visual disturbances or other less common symptoms (vertigo or déjà-vu). Tonic-clonic seizures were reported by almost all patients (88%), preceded by typical aura in 67% of cases. Seizures were precipitated by environmental noises in 8% of patients and were completely or almost completely controlled by antiepileptic treatment in the vast majority of cases (96%). The interictal EEG recordings showed epileptiform abnormalities or focal slow waves in 80% of patients, localized over the temporal regions, with marked left predominance and conventional 1,5T MRI scans were not contributory. By comparing these findings with those observed in families with LGI1 mutations, we did not observe significant differences except for a higher rate of left-sided EEG abnormalities in the RELN group.
Heterozygous RELN mutations cause a typical ADLTE syndrome, indistinguishable from that associated with LGI1 mutations.
描述7个与Reelin（RELN）突变相关的常染色体显性遗传性外侧颞叶癫痫（ADLTE）家系的临床表型，并将数据与我们系列中的12个携带LGI1突变的家系所观察到的数据进行比较。
在参与意大利癫痫联盟遗传学委员会一项为期14年（2000 - 2014年）合作研究的癫痫学家收集的40个意大利ADLTE家系中，发现7个（17.5%）携带杂合RELN突变。整个系列还包括12个（30%）携带LGI1突变的家系和21个（52.5%）未突变的家系。对RELN和LGI1突变家系的临床、神经生理学和神经放射学结果进行分析。
在属于7个RELN突变家系的28名受影响个体中，24名有足够的临床数据用于研究。在这些患者中，癫痫发作平均起始年龄为20岁，局灶性发作约71%以听觉先兆为特征，三分之一的患者伴有失语、视觉障碍或其他较不常见症状（眩晕或似曾相识感）。几乎所有患者（88%）都有强直阵挛发作，67%的病例有典型先兆。8%的患者发作由环境噪音诱发，绝大多数病例（96%）癫痫发作通过抗癫痫治疗得到完全或几乎完全控制。发作间期脑电图记录显示80%的患者有癫痫样异常或局灶性慢波，定位于颞区，明显以左侧为主，传统的1.5T磁共振成像扫描无诊断价值。通过将这些结果与LGI1突变家系中观察到的结果进行比较，我们未观察到显著差异，除了RELN组左侧脑电图异常发生率较高。
杂合RELN突变导致典型的ADLTE综合征，与LGI1突变相关的综合征难以区分。
