What distinguishes Dravet syndrome and Generalized Epilepsy with Febrile Seizures Plus (GEFS+)?

From the Guidelines

Dravet syndrome and Genetic Epilepsy with Febrile Seizures Plus (GEFS+) are distinguished primarily by their severity and clinical presentation, though they share genetic origins. Dravet syndrome is a more severe epileptic encephalopathy characterized by frequent, prolonged seizures beginning in the first year of life, often triggered by fever, followed by development of multiple seizure types including myoclonic, absence, and partial seizures. Children with Dravet syndrome typically experience developmental delays, cognitive impairment, and behavioral issues. In contrast, GEFS+ represents a milder phenotype with febrile seizures that may persist beyond age 6 and occasional afebrile seizures, but generally normal development. Both conditions are commonly associated with mutations in the SCN1A gene, which encodes a sodium channel subunit essential for neuronal function, but Dravet syndrome mutations typically cause complete loss of function while GEFS+ mutations cause partial dysfunction. Some key points to consider when differentiating between Dravet syndrome and GEFS+ include:

• Severity of seizures: Dravet syndrome is characterized by more frequent and severe seizures, while GEFS+ has milder seizures.
• Age of onset: Dravet syndrome typically begins in the first year of life, while GEFS+ may start at any age.
• Developmental impact: Dravet syndrome is associated with significant developmental delays and cognitive impairment, while GEFS+ typically has normal development.
• Treatment approaches: Dravet syndrome requires more aggressive management, including combinations of medications like stiripentol, valproate, clobazam, and dietary therapies, while GEFS+ often responds to standard antiepileptic medications or may not require long-term treatment, as noted in studies such as 1. It's worth noting that the provided evidence, such as 1, does not directly address the distinction between Dravet syndrome and GEFS+, but rather discusses the use of stiripentol in the treatment of Dravet syndrome. However, based on the available information and general medical knowledge, the primary distinction between Dravet syndrome and GEFS+ lies in their severity and clinical presentation.

From the Research

Key Differences between Dravet Syndrome and GEFS+

• Dravet syndrome is a severe infantile onset epilepsy syndrome with multiple seizure types, developmental slowing, and poor outcome, whereas GEFS+ refers to a familial epilepsy syndrome with a range of mild to severe phenotypes varying from classical febrile seizures to Dravet syndrome 2.
• Dravet syndrome is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments, often triggered by fever, infections, or vaccinations 3.
• GEFS+ has a more variable phenotype, with some patients experiencing only febrile seizures, while others may develop more severe epilepsy syndromes like Dravet syndrome 2.
• Both Dravet syndrome and GEFS+ can arise due to mutations of SCN1A, the gene encoding the alpha 1 pore-forming subunit of the sodium channel, but the type and location of the mutation can influence the severity of the phenotype 2, 4.
• Dravet syndrome is often associated with de novo truncation mutations in SCN1A, whereas GEFS+ is more commonly associated with missense mutations in SCN1A or other genes such as SCN1B and GABRG2 2.

Genetic Features

• More than 70% of patients with Dravet syndrome have mutations of SCN1A, including both truncation and missense mutations 2.
• In contrast, only 10% of GEFS+ families have SCN1A mutations, which are typically missense mutations 2.
• The phenotypic heterogeneity of GEFS+ is likely due to modifier genes, making it challenging to predict the clinical outcome based on the type of mutation 2, 4.

Clinical Implications

• Early recognition of Dravet syndrome is crucial, as aggressive control of seizures may improve developmental outcome 2.
• Treatment strategies for Dravet syndrome focus on balancing reduction of seizure burden with adverse effects of therapies, and may include medications such as clobazam, valproic acid, and stiripentol, as well as alternative therapies like the ketogenic diet and vagal nerve stimulation 5.
• Understanding the neuropathology of different SCN1A mutations may help predict the expected clinical phenotypes and inform the selection of best-fit treatments 4.