Endophenotype Strategy in Epilepsy Genetics

  • Dalila Pinto
  • Dorothée Kasteleijn-Nolst Trenité
  • Dick Lindhout

Despite being largely genetically determined, the genes involved in idiopathic generalized epilepsies (IGE) are mostly unknown. The difficulties in pinpointing the genes for common IGEs lie mainly in their underlying complex inheritance patterns and genetic heterogeneity within phenotype definitions. The different IGE syndromes are distinguished by combinations of absences, myoclonic seizures and generalized tonic-clonic seizures with characteristic ranges of age-at-onset. Photosensitivity or photoparoxysmal EEG response (PPR) is found in up to 50% of IGE syndromes, including myoclonic epilepsies and absence epilepsies. This increased co-morbidity of PPR with IGE compared to 1.4% in the general population, suggests that PPR may be involved in the predisposition for IGE. Consequently, it has been hypothesized that PPR may constitute a potential endophenotype for IGE, which could be useful to dissect the complexity of the IGEs. The criteria for using PPRs as a valid and useful endophenotype will be discussed, and examples given of its use in genome-wide linkage and association screens in large collections of multiplex PPR families and cases. Endophenotype approaches in epilepsy genetics, such as a PPR or imaging, offer great promise as an alternative or complement to the studies of categorical disease phenotypes.


Epilepsy photosensitivity photoparox-ysmal response PPR endophenotype genetics 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Dalila Pinto
    • 1
  • Dorothée Kasteleijn-Nolst Trenité
    • 2
    • 3
  • Dick Lindhout
    • 4
  1. 1.Research Fellow. Department of Medical Genetics. University Medical Center Utrecht Utrecht, the Netherlands; and Genetics and Genome Biology, The Center for Applied GeneticsThe Hospital of Sick ChildrenTorontoCanada
  2. 2.Professor Medical Genetics, University of Utrecht; Department of Medical GeneticsUniversity Medical CentreUtrechtthe Netherlands
  3. 3.Department of NeuroscienceProfessor Neuroscience, University of Rome “Sapienza”RomeItaly
  4. 4.Department of Medical GeneticsUniversity Medical Centre UtrechtUtrechtThe Netherlands

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