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Neurology 2003;60:410-414
© 2003 American Academy of Neurology

Phenotypic features of familial febrile seizures

Case-control study

Deb K. Pal, PhD MRCP, Steven L. Kugler, MD, David E. Mandelbaum, MD PhD and Martina Durner, MD

From the Clinical and Genetic Epidemiology Unit (Dr. Pal), Department of Psychiatry, and Division of Statistical Genetics (Drs. Pal and Durner), Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY; and Division of Child Neurology (Drs. Kugler and Mandelbaum), Department of Pediatrics, UMDNJ–Robert Wood Johnson Medical School, New Brunswick, NJ.

Address correspondence and reprint requests to Dr. Deb K. Pal, Clinical and Genetic Epidemiology Unit, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 24, Columbia University, New York, NY 10032; e-mail: dkp28{at}columbia.edu

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.




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[Abstract] [PDF]


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