Lack of SCN1A Mutations in Familial Febrile Seizures

Malacarne, Michela; Madia, Francesca; Gennaro, Elena Di; Vacca, Daniela; Güney, Ahmet İlter; Buono, Salvatore; Bernardina, Bernardo Dalla; Gaggero, R.; Gobbi, Giuseppe; Lispi, Maria Luisa; Malamaci, Daniela; Melideo, G.; Roccella, M; Sferro, C.; Tiberti, Alessandra; Vanadia, Francesca; Vigevano, Federico; Viri, Franco; Vitali, Maria Rosa; Bricarelli, Franca Dagna; Bianchi, Amedeo; Zara, Federico

doi:10.1046/j.1528-1157.2002.29301.x

Cited by 21 publications

(11 citation statements)

References 14 publications

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“…As epilepsy in relatives had the characteristics of idiopathic generalized epilepsy (IGE), the authors concluded that SMEI is genetically linked to FS and to other phenotypes of IGE. The identification of de novo SCN1A mutations in SMEI probands and the lack of SCN1A mutations in families with common forms of IGE (Escayg et al, 2001) or FS (Malacarne et al, 2002) challenged this view and suggested our investigation of the familial antecedents of FS and epilepsy in a homogeneous group of SMEI patients showing SCN1A mutations.…”

Section: Discussionmentioning

confidence: 99%

Familial Occurrence of Febrile Seizures and Epilepsy in Severe Myoclonic Epilepsy of Infancy (SMEI) Patients with SCN1A Mutations

et al. 2006

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Summary:Purpose: 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. Key Words: Severe myoclonic epilepsy of infancy-Voltage-gated sodium channel αsubunit type A-Genetics.

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Section: Discussionmentioning

confidence: 99%

Familial Occurrence of Febrile Seizures and Epilepsy in Severe Myoclonic Epilepsy of Infancy (SMEI) Patients with SCN1A Mutations

et al. 2006

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“…SCN1A mutations were initially found in large families with GEFS+ in 2000 (Escayg, 2000). A missense SCN1A mutation was reported in a family with children who experienced simple febrile convulsions (Mantegazza et al, 2005), but this mutation was considered to be a rare case (Malacarne et al, 2002). There was no comparison of the detection of SCN1A mutations in children under one year of age with FS who did and did not develop Dravet syndrome.…”

Section: Figurementioning

confidence: 99%

A Screening test for the prediction of Dravet syndrome before one year of age

et al. 2007

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SUMMARYPurpose: Our aim was to develop a screening test to predict Dravet syndrome before the first birthday based on the clinical characteristics of infants and the SCN1A mutation analysis. Methods: Ninety-six patients who experienced febrile seizures before the age of one were enrolled. The patients were divided into two groupsthe Dravet syndrome group (n = 46) and the nonDravet syndrome group (n = 50). We compared the clinical characteristics before one year of age of the two groups. We analyzed all coding exons of the SCN1A gene by the direct sequencing method. Scores from 0 to 3 were assigned to each risk factor based on the odds ratio and p-value. Results: An age of onset of febrile seizure ≤ 7 months, a total number of seizures ≥ 5, and prolonged seizures lasting more than 10 min. were regarded as significant risk factors for Dravet syndrome. Other factors highly predictive of this syndrome were hemiconvulsions, partial seizures, myoclonic seizures, and hot water-induced seizures. A total clinical score of six or above was the cutoff value indicating a high risk of Dravet syndrome. SCN1A missense and truncated mutations were detected significantly more often in the Dravet syndrome group than in the non-Dravet syndrome group. Discussion: This simple screening test was designed to be used by general pediatricians. It could help to predict Dravet syndrome before one year of age. If the sum of the clinical risk score is ≥ 6, then the performance of an SCN1A mutation analysis is recommended.

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“…3 Linkage studies in single rare pedigrees have yielded several mutations in sodium channel subunit genes, [4][5][6] but there is no evidence that these "private" mutations have a role in the causation of common FS. 7 Moreover, the phenotypes in these reported pedigrees are unusual, with many affected members, extended age at onset and offset, and partial seizures and afebrile seizure types sometimes interspersed. 8 This raises further questions about the extent of generalizability of these discoveries for common seizure disorders.…”

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confidence: 92%