title: Electroclinical features of a family with simple febrile seizures and temporal lobe epilepsy associated with SCN1A loss-of-function mutation.
abstract: OBJECTIVE
  To report in detail the electroclinical features of a large family in which we recently identified a missense mutation (M145T) of a well-conserved amino acid in the first transmembrane segment of domain I of the human SCN1A. We showed that the mutation is associated with a loss of SCN1A function.
  
  
  METHODS
  The family originates from southern Italy and contains 35 members spread over four generations. Of the 14 affected individuals, the 13 still living members (7 males, mean age 36.6 +/- 20.4) underwent a complete electroclinical evaluation.
  
  
  RESULTS
  All 13 affected family members had febrile seizures (FS) up to the age of 6 years. Age at onset of FS ranged from 5 to 45 months with a mean age of 12.8 +/- 12.9 months. One of the 13 was affected by post-traumatic epilepsy. Three of the 13 later developed temporal lobe epilepsy (TLE) with both simple focal seizures, and also very rare focal complex or nocturnal secondary generalized tonic-clonic seizures. In two of the three patients who later developed TLE, the MRI studies revealed mesial temporal sclerosis.
  
  
  CONCLUSIONS
  Our findings illustrate that SCN1A mutations can cause simple FS associated with TLE, which differ from the characteristic clinical spectrum of GEFS+. It is open to conjecture if this unusual phenotype might at least in part be related to the fact that M145T is the first missense mutation found in DIS1 of SCN1A.
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Colosimo
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambardella
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mantegazza
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Labate
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Raffaela
authors.initials: R
authors.lastname: Rusconi
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Schiavon
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Ferdinanda
authors.initials: F
authors.lastname: Annesi
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Rita R
authors.initials: RR
authors.lastname: Cassulini
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Carrideo
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Chifari
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Canevini
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Canger
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Franceschetti
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Annesi
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Wanke
authors.affiliation: Institute of Neurology, University Magna Graecia, CatanzaroInstitute of Neurological Sciences, National Research Council, Piano Lago di Mangone, CosenzaDepartment of Neurophysiopathogy, Istituto Neurologico C. Besta, MilanoDepartment of Biotechnologies and Biosciences, University of Milano Bicocca, MilanoCenter for Child Epilepsy, Azienda Ospedaliera "Fatebenefratelli e Oftalmico," MilanoRegional Centre of Epilepsy, San Paolo Hospital, Milano, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Quattrone
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D001921:Brain / Q000473:pathology; D002648:Child; D004569:Electroencephalography / Q000706:statistics & numerical data; D004833:Epilepsy, Temporal Lobe / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D005190:Family; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D003294:Seizures, Febrile / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels