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CLINICAL OVERVIEW

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Febrile seizures (FS) are the most common type of convulsion among pediatric patients. The prevalence of FS varies between different populations, affecting, for example, an estimated 2%–5% of European and North American children and 6%–9% of children from Japan. In a large registry-based study of febrile seizures in children born in Denmark between 1977 and 2004, 50% experienced their first febrile seizure between 6 and 18 months of age, and 93% before the age of 48 months.1

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Febrile seizures are classified as either simple or complex in nature. Simple FS are defined as short (<15 minutes), generalized tonic, clonic, or tonic–clonic seizures that occur during the course of a febrile illness2,3,4; approximately 80%–90% of FS are simple febrile convulsions.5 Complex FS consist of either focal or generalized seizures that are prolonged (>15 minutes) or recurrent over a 24-hour period. Febrile seizures that persist for longer than 30 minutes or that involve multiple shorter seizures without return to a baseline level of consciousness are termed febrile status epilepticus.6

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RISK FACTORS

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Febrile seizures, whether simple or complex, generally occur in the context of an illness that causes a fever of at least 38.0°C.3 FS tend to be seen in conjunction with common infections, such as upper respiratory tract infections, otitis media, and gastrointestinal disorders; however, there is no specific infectious agent connected to febrile seizures. FS associated with fevers secondary to immunizations are also common. In this setting, the seizure typically occurs within 48 hours after administration of the immunization.7 Most often, both simple and complex FS occur early in the course of an illness or during the initial rise in body temperature, but the seizure may also precede the onset of fever.

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In addition to fever, FS are precipitated by other environmental and/or genetic factors that remain largely unidentified. Vestergaard and Christensen1 observed that low birth weight and short gestational ages were significant risk factors for FS; however, there was no association between birth weight, birth order, or 1- or 5-minute Apgar scores and an increased risk for FS in a study of disease-discordant twins.8 Moreover, prenatal exposure to other common insults, such as maternal smoking, alcohol or coffee consumption, and stress, appear to have little to no effect on the incidence of FS.1

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Twin and family studies reveal that genetic factors play an important role in FS, and that there are different modes of inheritance. Large pedigrees with recurrent FS are often consistent with a model of autosomal dominant inheritance with reduced penetrance, although the majority of cases are likely due to more complex, polygenic inheritance. Genetic linkage analysis of FS families points to at least 10 loci that are suspected of harboring FS genes (reviewed in9), yet there has been little progress toward identifying the actual disease-causing genes.

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Ion channels play an important role in the regulation of neuronal excitability, and ...

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