Infantile Epilepsy: Dravet Syndrome, SFM1 - SCN1A

Clinical Features

Epilepsies caused by mutations in the SCN1A gene comprise a wide clinical spectrum of epilepsies that can vary greatly in manifestation and severity, even within a single family. In many cases, the first seizure occurs in association with an infection (with or without fever) or vaccination. Strong emotions such as great joy or fear can also trigger seizures.
SCN1A mutations have been described for various types of seizures and/or epilepsy syndromes, especially for an age of onset in the first 24 months. These most often include:

Dravet Syndrome and/or SMEI (severe myoclonic epilepsy in infancy)
SMEB (severe myoclonic epilepsy, borderline)
PMEI (polymorphic myoclonic epilepsy in infancy)
Generalized epilepsy with febrile seizures plus (GEFS+)
Infantile partial seizures with variable foci, seizures of infancy, cryptogenic focal epilepsy, severe infantile multifocal epilepsy

More rare cases include:

Myoclonic-astatic epilepsy (MAE, Doose syndrome)
Lennox-Gastaut Syndrome (LGS)
Infantile spasms
West Syndrome
Febrile seizures (FS)
Vaccination-associated encephalopathy with seizures

Mutations in the SCN1A gene also lead to Familial Hemiplegic Migraines (FHM3).
Initial clinical suspicion of disease-causing mutations in the SCN1A gene follows in cases of infantile epilepsy in combination with one or more family member with epilepsy, especially with the presence of various seizure types in the family, febrile seizures prior to 1 or after 6 years of age or complex febrile seizures and febrile Status epilepticus and/or febrile seizures followed by unprovoked afebrile seizures.

The use of sodium channel blockers in treating the disease may aggravate clinical symptoms.

Genetic Information

The SCN1A gene is located on chromosome 2 (2q24) and codes for a sodium channel protein type 1 subunit alpha). Epilepsies caused by mutations in the SCN1A gene follow an autosomal dominant pattern of inheritance and have incomplete penetrance. New mutations are possible, especially in severe forms of the disease.