Electroclinical features of a family with simple febrile seizures and temporal lobe epilepsy associated with SCN1A loss-of-function mutation.
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.
Colosimo
Eleonora
E
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.
Gambardella
Antonio
A
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.
Mantegazza
Massimo
M
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.
Labate
Angelo
A
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.
Rusconi
Raffaela
R
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.
Schiavon
Emanuele
E
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.
Annesi
Ferdinanda
F
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.
Cassulini
Rita R
RR
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.
Carrideo
Sara
S
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.
Chifari
Rosanna
R
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.
Canevini
Maria Paola
MP
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.
Canger
Raffaele
R
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.
Franceschetti
Silvana
S
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.
Annesi
Grazia
G
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.
Wanke
Enzo
E
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.
Quattrone
Aldo
A
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.
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*
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels