Phenotypic features of familial febrile seizures: case-control study.
OBJECTIVE
To identify phenotypic features of febrile seizures that can be used to reduce heterogeneity and thereby increase power in linkage analysis.


BACKGROUND
Despite exciting discoveries in several rare pedigrees, the genetic basis of common febrile seizures remains a mystery. The major drawback of studying common febrile seizure disorder is etiologic and genetic heterogeneity. A linkage sample must therefore be classified a priori on phenotypic criteria likely to reflect genetically homogeneous subgroups.


METHODS
Eighty-three cases (children with one or more febrile seizure plus first-degree family history of febrile seizures) and 101 controls (children with one or more febrile seizure but no first-degree family history of febrile seizures) were compared for association of phenotypic features in an unmatched case-control design. Odds ratios were calculated using univariate and multivariate methods.


RESULTS
Recurrent febrile seizures was the only phenotypic feature significantly associated with first-degree family history of febrile seizures (OR 2.1, 95% CI 1.15 to 3.88). First-degree family history and later occurrence of afebrile seizures (OR 3.47, 95% CI 0.94 to 12.78) were independently associated with recurrent febrile seizures. Complex features did not show familial aggregation.


CONCLUSIONS
The authors suggest recurrent and afebrile seizures as criteria on which to subgroup a linkage sample. These subgroups will not be evident at the time of the initial febrile seizure. Meticulous and prospective collection of phenotypic and family data are recommended.
Pal
Deb K
DK
Clinical and Genetic Epidemiology Unit, Department of Psychiatry, and Division of Statistical Genetics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. dkp28@columbia.edu
Kugler
Steven L
SL
Mandelbaum
David E
DE
Durner
Martina
M
D000293:Adolescent; D000328:Adult; D001831:Body Temperature; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D006801:Humans; D007223:Infant; D007407:Interviews as Topic; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D012008:Recurrence; D012307:Risk Factors; D003294:Seizures, Febrile / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D017678:Sex Distribution; D014481:United States / Q000453:epidemiology