Generalised Epilepsy with Febrile Seizures Plus (GEFS+)
GEFS+ is a family of genetic epilepsy syndromes with a wide range of seizure types and outcomes. The “plus” in the name signifies that the seizures extend beyond typical febrile seizures. Unlike many other epilepsy syndromes, GEFS+ is not a single diagnosis but a spectrum of conditions.
Presentation and Clinical Features
Age of Onset: Onset is in early childhood, typically before the age of 6.
Seizure Characteristics: The hallmark is a history of febrile seizures that are atypical. This can mean they have an early onset (before 6 months), are unusually prolonged, recur frequently, are unilateral, or continue beyond the age of 6. The “plus” refers to the occurrence of afebrile seizures in addition to the febrile ones. These can include:
Generalized tonic-clonic seizures
Focal seizures
Myoclonic seizures
Absence seizures
Genetics: GEFS+ is an autosomal dominant disorder with incomplete penetrance. It’s often caused by mutations in genes that encode sodium or GABA receptors, such as SCN1A (which is also implicated in Dravet Syndrome). The same gene mutation can lead to different phenotypes within a family, from simple febrile seizures to severe epileptic encephalopathies.
Development and Cognition: A key distinguishing feature of GEFS+ is that, unlike more severe epileptic encephalopathies, development and cognition are typically not affected.
Investigations
Diagnosis: The diagnosis is primarily based on a detailed clinical history of the seizure types, their triggers, and the presence of similar epilepsy in family members.
EEG: The interictal (between seizures) EEG may be normal. When abnormalities are present, they are often generalized spike-and-wave discharges, which are more likely to be seen with sleep deprivation.
Genetic Testing: Genetic testing is not required to make the clinical diagnosis but can be valuable for confirming a specific aetiology and for genetic counselling.
Management and Prognosis
Prognosis: The prognosis is generally good, with seizures typically remitting by puberty. The risk of long-term neurodevelopmental problems is low.
Treatment: The approach to management is individualised based on the seizure frequency and type.
Febrile Seizures Only: For those with infrequent febrile seizures, medication may not be necessary. Rescue medication, such as buccal midazolam, should be provided for prolonged seizures.
Afebrile Seizures: For those with more frequent or afebrile seizures, regular anti-epileptic drugs (AEDs) are considered. Valproate, Levetiracetam, Lamotrigine, and Clobazam are effective choices.
Medications to Avoid: As GEFS+ has some genetic overlap with Dravet Syndrome, some clinicians may avoid sodium channel blockers like carbamazepine and lamotrigine, particularly if myoclonic seizures are present.
Genetic Counselling: Due to the wide phenotypic spectrum, genetic counselling is essential for affected families to help them understand the risks for future children.
Differentiation from Dravet Syndrome: It is crucial to correctly differentiate GEFS+ from more severe epileptic encephalopathies like Dravet Syndrome or Doose Syndrome. This distinction is critical as it guides management and shapes the long-term prognosis. Patients with GEFS+ do not have the progressive developmental decline seen in Dravet Syndrome.