Familial occurrence of febrile seizures and epilepsy in severe myoclonic epilepsy of infancy (SMEI) patients with SCN1A mutations.
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.
Mancardi
Maria Margherita
MM
Laboratory of Neurogenetics, Unit of Muscular and Neurodegenerative Disease, Institute G. Gaslini, Genova, Italy.
Striano
Pasquale
P
Gennaro
Elena
E
Madia
Francesca
F
Paravidino
Roberta
R
Scapolan
Sara
S
Dalla Bernardina
Bernardo
B
Bertini
Enrico
E
Bianchi
Amedeo
A
Capovilla
Giuseppe
G
Darra
Francesca
F
Elia
Maurizio
M
Freri
Elena
E
Gobbi
Giuseppe
G
Granata
Tiziana
T
Guerrini
Renzo
R
Pantaleoni
Chiara
C
Parmeggiani
Antonia
A
Romeo
Antonino
A
Santucci
Margherita
M
Vecchi
Marilena
M
Veggiotti
Pierangelo
P
Vigevano
Federico
F
Pistorio
Angela
A
Gaggero
Roberto
R
Zara
Federico
F
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*
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels