title: Familial occurrence of febrile seizures and epilepsy in severe myoclonic epilepsy of infancy (SMEI) patients with SCN1A mutations.
abstract: OBJECTIVE
  The role of the familial background in severe myoclonic epilepsy of infancy (SMEI) has been traditionally emphasized in literature, with 25-70% of the patients having a family history of febrile seizures (FS) or epilepsy. We explored the genetic background of SMEI patients carrying SCN1A mutations to further shed light on the genetics of this disorder.
  
  
  METHODS
  We analyzed the occurrence of FS and epilepsy among first- and second-degree relatives (N = 867) of 74 SMEI probands with SCN1A mutations (70 de novo, four inherited) and compared data with age-matched and ethnically matched control families. Familial clustering and syndromic concordance within the affected relatives in both groups were investigated.
  
  
  RESULTS
  The frequency of FS or epilepsy in relatives of SMEI patients did not significantly differ from that in controls (FS: 13 of 867 vs. 12 of 674, p = 0.66; epilepsy: 15 of 867 vs. six of 674, p = 0.16). Different forms of epilepsy were identified in both relatives of SMEI probands and controls. Twenty-eight relatives with FS and epilepsy were distributed in 20 (27%) of 74 SMEI families; among the controls, 18 affected relatives were clustered in 13 (18.5%) of 70 families. No pedigree showed several affected members, including the four with inherited mutations.
  
  
  CONCLUSIONS
  A substantial epileptic family background is not present in our SMEI patients with SCN1A mutations. These data do not confirm previous observations and would not support polygenic inheritance in SMEI. The investigation of the family background in additional series of SMEI patients will further shed light on the genetics of this syndrome.
authors.affiliation: Laboratory of Neurogenetics, Unit of Muscular and Neurodegenerative Disease, Institute G. Gaslini, Genova, Italy.
authors.forename: Maria Margherita
authors.initials: MM
authors.lastname: Mancardi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.forename: Elena
authors.initials: E
authors.lastname: Gennaro
authors.forename: Francesca
authors.initials: F
authors.lastname: Madia
authors.forename: Roberta
authors.initials: R
authors.lastname: Paravidino
authors.forename: Sara
authors.initials: S
authors.lastname: Scapolan
authors.forename: Bernardo
authors.initials: B
authors.lastname: Dalla Bernardina
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Amedeo
authors.initials: A
authors.lastname: Bianchi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Capovilla
authors.forename: Francesca
authors.initials: F
authors.lastname: Darra
authors.forename: Maurizio
authors.initials: M
authors.lastname: Elia
authors.forename: Elena
authors.initials: E
authors.lastname: Freri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gobbi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Granata
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Chiara
authors.initials: C
authors.lastname: Pantaleoni
authors.forename: Antonia
authors.initials: A
authors.lastname: Parmeggiani
authors.forename: Antonino
authors.initials: A
authors.lastname: Romeo
authors.forename: Margherita
authors.initials: M
authors.lastname: Santucci
authors.forename: Marilena
authors.initials: M
authors.lastname: Vecchi
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Veggiotti
authors.forename: Federico
authors.initials: F
authors.lastname: Vigevano
authors.forename: Angela
authors.initials: A
authors.lastname: Pistorio
authors.forename: Roberto
authors.initials: R
authors.lastname: Gaggero
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
mesh_terms: D004831:Epilepsies, Myoclonic / Q000453:epidemiology / Q000235:genetics*; D004827:Epilepsy / Q000453:epidemiology / Q000235:genetics*; D005190:Family; D006801:Humans; D009154:Mutation / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D003294:Seizures, Febrile / Q000453:epidemiology / Q000235:genetics*; 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