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Published on: July 12, 2021
Pedigree analysis in families with febrile seizures
W G Johnson1, S L Kugler, E S Stenroos
1Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey, USA.
Insights
Febrile seizures, common in children, show strong familial patterns. Autosomal dominant inheritance with reduced penetrance is the likely mode, suggesting genetic factors influence seizure occurrence.
Area of Science:
- Pediatrics
- Genetics
- Neurology
Background:
- Febrile seizures affect 2-5% of North American children, representing the most common seizure type.
- Understanding the genetic basis of febrile seizures is crucial for diagnosis and management.
Purpose of the Study:
- To investigate the inheritance patterns and genetic transmission of febrile seizures.
- To estimate the penetrance of the genetic factors involved in febrile seizures.
Main Methods:
- A systematic pedigree study was conducted on probands with febrile seizures.
- Statistical analysis, including mode of inheritance and penetrance calculations, was performed on family data.
- Simulated lod scores were used to assess the power for linkage studies.
Main Results:
- 77% of probands in a selected, high-severity population had multiple affected family members.
- Autosomal dominant inheritance with reduced penetrance (estimated at 0.64) best explained the inheritance pattern in multicase families.
- X-linked and mitochondrial inheritance patterns were not supported by the data.
Conclusions:
- Febrile seizures exhibit a significant familial aggregation, strongly suggesting a genetic component.
- Autosomal dominant inheritance with reduced penetrance is the most probable mode of inheritance.
- Further genetic studies with dense marker maps and additional families are needed to confirm linkage, especially considering potential heterogeneity.
Abstract:
Febrile seizures are the most common form of seizures, occurring in an estimated 2-5% of North American children. We carried out a systematic pedigree study of febrile seizure probands. Forty of 52 probands (77%) in a referral population selected for increased severity had more than one case per family: one family had 10 cases, one family had 7, 3 families had 6, 2 had 5, 3 had 4, 13 had 3, and 17 had 2 cases. Mode of inheritance in the multicase families best fit the hypothesis of autosomal dominance with reduced penetrance. Polygenic inheritance could not be excluded for some of the smaller families. There was no support for X-linked or mitochondrial inheritance. Penetrance was calculated to be 0.64. Because the cases were selected for increased severity, this represents a useful estimate of the upper limit of penetrance and is in agreement with twin studies. Simulated lod scores showed adequate power for a linkage study in the absence of heterogeneity. Individual families had simulated average lod scores as high as 2.1. However, with potential heterogeneity, assuming only 70% of families share the same disease locus, average lod scores were marginal, and a high density map of marker loci and additional families would be required to document linkage.
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