Genetic alterations in the SCN1A gene coding for the α-subunit of the neuronal voltage-gated sodium ion channel, type 1 (NaV 1.1), is associated with a spectrum of seizure-related disorders in human, ranging from a relatively milder form of febrile seizures to a more severe epileptic condition known as the Dravet syndrome.
It is suspected that mosaic mutations of SCN1A may cause other types of familial epilepsies with febrile seizures (FS), which are more common clinically.
Failure to find association between febrile seizures and SCN1Ars3812718 polymorphism in south Indian patients with mesial temporal lobe epilepsy and hippocampal sclerosis.
Recently, there have been sporadic case reports of epilepsy/febrile seizure and acute encephalopathy with a neuronal sodium channel alpha 1 subunit (SCN1A) mutation.
Most mutations in SCN1A-related epilepsies are novel and when an infant presents with febrile seizures (FS) it is uncertain if they will have simple FS, FS+, or develop a severe epilepsy such as Dravet syndrome.
We postulated that earlier onset of febrile seizures in the febrile seizure (FS) and febrile seizure plus (FS+) phenotypes may occur in the presence of a SCN1A mutation.
One patient has a family history consistent with the family epilepsy syndrome diagnosis of GEFS+, whilst the second has a de novo SCN1A mutation in the setting of "severe" Febrile Seizures.
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.
Extensive genetic studies have demonstrated that various loci are responsible for familial FS, and the FEB3 autosomal-dominant locus has been identified on chromosome 2q23-24, where the SCN1A gene is mapped.
These results illustrate that the clinical spectrum of SCN1A mutations ranges from febrile seizures, febrile seizures plus, over a milder type to the classical form of severe myoclonic epilepsy in infancy, and confirm the clinical experience that severe myoclonic epilepsy in infancy is the most severe form on this spectrum.
By performing an association study, we used single nucleotide polymorphisms to investigate the distribution of genotypes of SCN1A in patients with FCs.