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Severe autosomal dominant nocturnal frontal lobe epilepsy associated with psychiatric disorders and intellectual disability
Author(s) -
Derry Christopher P.,
Heron Sarah E.,
Phillips Fiona,
Howell Stephen,
MacMahon Jacinta,
Phillips Hilary A.,
Duncan John S.,
Mulley John C.,
Berkovic Samuel F.,
Scheffer Ingrid E.
Publication year - 2008
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2008.01652.x
Subject(s) - epilepsy , intellectual disability , frontal lobe , psychiatry , psychology , genetic linkage , candidate gene , medicine , genetics , gene , biology
Summary Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a relatively benign epilepsy syndrome with few comorbidities. Here we describe two families with unusually severe ADNFLE, with associated psychiatric, behavioral, and cognitive features. Detailed clinical data on 17 affected individuals were obtained, and genotyping of microsatellite markers, linkage analysis, and sequencing of candidate genes was performed. The severe ADNFLE phenotype in these families was often refractory to treatment, with status epilepticus occurring in 24% of subjects. Psychiatric or behavioral disorders occurred in 53%, with intellectual disability in 24%, and developmental regression in two individuals. No mutations were identified in α4, α2, or β2 nAChR subunits. In one family there was evidence of linkage to a region of 15q24 without nAChR subunit genes. In conclusion, severe ADNFLE has significant medical, psychiatric, and intellectual morbidity. The molecular basis of severe ADNFLE is unknown but may involve non‐nAChR‐related mechanisms.