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Prevalence is unknown but hundreds of cases have been described in the literature.

Phenotypes in patients can be variable, ranging from simple FS to epileptic encephalopathies including MAE and DS. Disease onset is variable. FS plus (FS+) is the characteristic phenotype seen in most GEFS+ families, described as febrile seizures that persist beyond the age of 6 or that occur with other afebrile seizure types including generalized tonic-clonic seizures, myoclonic, or absence seizures that usually remit by late childhood or early adolescence. Occasional seizures in adulthood are possible. Partial seizure types can also be observed.

Mutations in SCN1A (2q24.3) (most commonly) and SCN1B (19q13.12) have been identified as causal in several families with GEFS+. These genes encode two subunits of the neuronal sodium channel. Other causal mutations include those in the gamma 2 subunit (GABRG2) gene (5q34). SCN2A (2q24.3), SCN9A (2q24), and GABRD (1p36.3) have been suggested as possible susceptibility genes for GEFS+.

GEFS+ is diagnosed clinically through the seizure type of the patient and the family history. Molecular genetic testing can confirm the diagnosis.

Differential diagnoses include other genetic epilepsies such as benign familial infantile seizures (due to PRRT2 mutations) or encephalopathy due to GLUT1 deficiency (see these terms) or a sporadic epilepsy caused by injury or infections.

Given the broad phenotypic range of known GEFS+ mutations, prenatal diagnosis is usually not performed.

In most large families, GEFS+ is inherited in an autosomal dominant manner, often with incomplete penetrance. In other families it follows complex inheritance where several genes or environmental factors are thought to be involved. Genetic counseling is possible in families with a known disease causing mutation. However, precise phenotypes cannot be predicted as wide phenotypic variability is seen within families.

As most patients with GEFS+ have a mild phenotype, treatment may not be necessary. Seizure control with antiepileptic drugs is essential in patients with recurrent seizures. The drugs mainly used include valproic acid, benzodiazepines (i.e. clobazam), ethosuximide, levetiracetam and topiramate. Given the relatedness to DS, lamotrigine and phenytoin may not be considered. Temporal lobe surgery resulted in a positive outcome in two patients with GEFS+. Regular follow-up and neuropsychological evaluations are recommended along with electroencephalographic monitoring when a new seizure pattern is suspected. In patients with active epilepsy, activities where a seizure could lead to injury or death should be avoided.

The overall prognosis depends on the exact phenotype within the GEFS+ spectrum. In patients with mild phenotypes (FS, FS+) seizures often remit by adolescence. Patients with more severe phenotypes may require life-long treatment and may have lasting neurocognitive sequelae.