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Epidemiology
and Clinical Features
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A febrile seizure is defined by ILAE (International League Against
Epilepsy) as “a seizure in association with absence of
an infection (of the central nervous system) or acute electrolyte
imbalance in children older than 1 month of age, without prior non-febrile
seizures.”1 Febrile seizures are most
commonly seen between 6 months and 5 years, with a peak incidence
of approximately 18 months.2 Simple febrile seizures
are relatively brief (< 15 minutes), generalized, and do not
recur during the same febrile illness. In contrast, complex febrile
seizures have focal features, long duration, or recurrence within
24 hours. Prior neurological condition is not part of this classification.1
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The prevalence of febrile seizures is 2% to 4% in
the United States and Western Europe, and higher in Japan at 9% to 10%,
and Guam at 14%. The highest incidence of febrile seizures
is at approximately 18 months of age.2 Febrile
seizures tend to be more common during winter months, when children
are prone to have systemic illnesses.
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Risk factors for febrile convulsions include family history,
daycare attendance, and underlying developmental abnormality.3 However,
most children with febrile convulsions are developmentally normal
and do not have any prior brain insults.
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Most patients have simple febrile seizures, and the seizures
are often seen shortly after onset of fever; many febrile seizures
occur before parents are aware that the child has a fever. Certain
childhood diseases, such as roseola from human herpes virus-6 infection,
appear to be more prone to be associated with febrile seizures.4,5
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Etiology/Genetic
Factors
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Susceptibility to febrile convulsions appears to be strongly
influenced by genetic factors. Approximately 25% to 40% of
affected children have a positive family history, and siblings have
a 9% to 22% risk for febrile seizures.6 Such
observations support the concept that susceptibility to febrile
seizures is the result of the interaction of several genes. Linkage studies
have identified many loci associated with febrile seizures. These
loci include 8q13-q21 (FEB1), 19p (FEB2), 2q23-q24 (FEB3), 5q14-q15
(FEB4), 6q22-q24 (FEB5), and 18p11 (FEB6).7In
particular, there are families with strong autosomal-dominant penetrance
of febrile seizures, some members with febrile seizures beyond the
typical age, even some with epilepsy (mostly generalized); this
condition has been described as generalized epilepsy with febrile
seizure plus (GEFS Plus)8 or autosomal dominant epilepsy
with febrile seizures (ADEFS).9 Some of these have been
associated with mutations in alpha 1, alpha 2, and beta 1 subunits
of the sodium channel (SCN1A, SCN2A, and SCN1B), or gamma-2 subunit
of the GABAA receptor (GABRG2).7
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History and careful physical and neurological examination will
be necessary to identify the source of fever. The main concern in
children with febrile seizures is to evaluate for infection of the
central nervous system, such as ...