Abstract
ObjectiveTo 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.MethodsOut 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.ResultsOut 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 20 years, 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.SignificanceHeterozygous RELN mutations cause a typical ADLTE syndrome, indistinguishable from that associated with LGI1 mutations.
Highlights
Following a collaborative study promoted by the Genetic Commission of the Italian League against Epilepsy, a large number of Autosomal Dominant Lateral Temporal Lobe Epilepsy (ADLTE) families have been collected over the time and only one-third of them have been associated with leucine-rich glioma inactivated 1 (LGI1) mutations [5]
We analyzed the clinical features of 7 RELN mutated families [6] and compared the results with those observed in 12 LGI1 mutated pedigrees [5,13]
In this paper we have described the clinical, EEG, and MRI findings of 7 ADLTE pedigrees associated with heterozygous RELN mutations, which had been reported in detail elsewhere by our group [5,6,13]
Summary
The affected patients show normal neurological and cognitive status, normal conventional MRI, and belong to families where one or more members show a similar phenotype with evidence of autosomal dominant transmission. This condition has been associated with leucine-rich glioma inactivated 1 (LGI1) gene mutations [3,4]. Following a collaborative study promoted by the Genetic Commission of the Italian League against Epilepsy, a large number of ADLTE families have been collected over the time and only one-third of them have been associated with LGI1 mutations [5]
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