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Febrile Seizure Plus and PCDH19-Related Epilepsy Syndromes

Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. Practically, a patient has epilepsy if having two unprovoked seizures more than 24 hours apart, one unprovoked seizure and significant risk of another seizure, or epilepsy syndrome. Seizures induced by fever do not therefore fit this classification. An initial febrile seizure may therefore cause a false sense of security in children who evolve to febrile seizure plus syndromes. Sodium channel defects seem to predominate as the main causative factor for febrile seizure plus syndromes. More severe pathological variants, such as Dravet's syndrome, have phenotypic similarities to other fever-associated epileptic encephalopathies, including those caused by mutations in protocadherin 19 (PCDH19). The clinical presentations, investigational studies, and management of febrile seizure plus syndrome, as well as epilepsies associated with PCDH19 mutations will be reviewed.