title: The clinical phenotype of autosomal dominant lateral temporal lobe epilepsy related to reelin mutations.
abstract: 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.
authors.affiliation: IRCCS - Institute of Neurological Sciences of Bologna, Unit of Neurology, Bellaria Hospital, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Michelucci
authors.affiliation: Department of Neurology and Psychiatry, University of Rome "Sapienza", Policlinico Umberto 1° Hospital, Roma, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pulitano
authors.affiliation: Department of Neurological Sciences, University of Rome "Sapienza," Roma, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Di Bonaventura
authors.affiliation: C. Besta Foundation Neurological Institute, Milano, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Binelli
authors.affiliation: Neurology Clinic, University of Bari, Bari, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Luisi
authors.affiliation: IRCCS - Institute of Neurological Sciences of Bologna, Unit of Neurology, Bellaria Hospital, Bologna, Italy. Electronic address: elena.pasini@isnb.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Pasini
authors.affiliation: Department of Neurological Sciences, Federico II University, Napoli, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Striano
authors.affiliation: Muscular and Neurodegenerative Disease Unit, Institute "G. Gaslini," University of Genova, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.affiliation: Child and Adolescent Neuropsychiatry, Medical School, University of Salerno, Italy.
authors.forename: Giangennaro
authors.initials: G
authors.lastname: Coppola
authors.affiliation: Neurology Clinic, University of Bari, Bari, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: La Neve
authors.affiliation: Department of Neurological Sciences, University of Rome "Sapienza," Roma, Italy.
authors.forename: Anna Teresa
authors.initials: AT
authors.lastname: Giallonardo
authors.affiliation: Department of Neurology and Psychiatry, University of Rome "Sapienza", Policlinico Umberto 1° Hospital, Roma, Italy.
authors.forename: Oriano
authors.initials: O
authors.lastname: Mecarelli
authors.affiliation: Section of Padua, Institute of Neurosciences, Consiglio Nazionale delle Ricerche, Padova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Serioli
authors.affiliation: Section of Padua, Institute of Neurosciences, Consiglio Nazionale delle Ricerche, Padova, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Dazzo
authors.affiliation: Porto Conte Ricerche, Alghero, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Fanciulli
authors.affiliation: Section of Padua, Institute of Neurosciences, Consiglio Nazionale delle Ricerche, Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Nobile
mesh_terms: D000328:Adult; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D017034:Epilepsy, Frontal Lobe / Q000175:diagnosis / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*; D012893:Sleep Wake Disorders / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases
keywords: ADLTE; ADPEAF; Auditory auras; LGI1; RELN; Reelin