Linkage analysis and disease models in benign familial infantile seizures: A study of 16 families

Pasquale Striano, Maria Luisa Lispi, Elena Gennaro, Francesca Madia, Monica Traverso, Laura Bordo, Paolo Aridon, Filippo Martinelli Boneschi, Baldassare Barone, Bernardo Dalla Bernardina, Amedeo Bianchi, Giuseppe Capovilla, Pasquale De Marco, Olivier Dulac, Roberto Gaggero, Antonio Gambardella, Rima Nabbout, Jean François Prud'homme, Ruth Day, Francesca VanadiaMarilena Vecchi, Pierangelo Veggiotti, Federico Vigevano, Maurizio Viri, Carlo Minetti, Federico Zara

Research output: Contribution to journalArticle

Abstract

Purpose: Benign familial infantile seizures (BFIS) is a genetically heterogeneous condition characterized by partial seizures, onset age from 3 to 9 months, and favorable outcome. BFIS loci were identified on chromosomes 19q12-13.1 and 16p12-q12, allelic to infantile convulsions and choreathetosis. The identification of SCN2A mutations in families with only infantile seizures indicated that BFNIS and BFIS may show overlapping clinical features. Infantile seizures also were in a family with familial hemiplegic migraine and mutations in the ATP1A2 gene. We have examined the heterogeneous genetics of BFIS by means of linkage analysis. Methods: Sixteen families were examined. Probands underwent neurologic examination, at least one EEG recording, and, when possible, brain CT and MRI. Clinical information about relatives was collected. Families with SCN2A or ATP1A2 mutations were excluded from the study. Chromosome 16p and 19q loci were examined by linkage analysis using two models that differed in penetrance rate. Genetic heterogeneity was evaluated with both models. Results: Clinical information was available for 124 members of affected families. BFIS was diagnosed in 69 subjects. One patient without BFIS had a single febrile seizure, and another had rare episodes of paroxysmal dystonia. Evidence of linkage was obtained only for chromosome 16. Moreover, the high penetrance allowed the identification of genetic heterogeneity. Conclusions: Our data confirm the relevance of the chromosome 16 locus in BFIS and suggest the presence of an additional locus. This study shows that the genetic model used affects the outcome of linkage analysis.

Original languageEnglish
Pages (from-to)1029-1034
Number of pages6
JournalEpilepsia
Volume47
Issue number6
DOIs
Publication statusPublished - Jun 2006

Keywords

  • BFIS
  • Infantile seizures
  • Linkage analysis
  • Paroxysmal choreoathetosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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    Striano, P., Lispi, M. L., Gennaro, E., Madia, F., Traverso, M., Bordo, L., Aridon, P., Boneschi, F. M., Barone, B., Bernardina, B. D., Bianchi, A., Capovilla, G., De Marco, P., Dulac, O., Gaggero, R., Gambardella, A., Nabbout, R., Prud'homme, J. F., Day, R., ... Zara, F. (2006). Linkage analysis and disease models in benign familial infantile seizures: A study of 16 families. Epilepsia, 47(6), 1029-1034. https://doi.org/10.1111/j.1528-1167.2006.00521.x