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De novo SCN 1A pathogenic variants in the GEFS + spectrum: Not always a familial syndrome
Author(s) -
Myers Kenneth A.,
Burgess Rosemary,
Afawi Zaid,
Damiano John A.,
Berkovic Samuel F.,
Hildebrand Michael S.,
Scheffer Ingrid E.
Publication year - 2017
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/epi.13649
Subject(s) - dravet syndrome , epilepsy , phenotype , epilepsy syndromes , medicine , febrile seizure , missense mutation , genetics , biology , pediatrics , gene , psychiatry
Summary Genetic epilepsy with febrile seizures plus ( GEFS +) is a familial epilepsy syndrome characterized by heterogeneous phenotypes ranging from mild disorders such as febrile seizures to epileptic encephalopathies ( EE s) such as Dravet syndrome ( DS ). Although DS often occurs with de novo SCN 1A pathogenic variants, milder GEFS + spectrum phenotypes are associated with inherited pathogenic variants. We identified seven cases with non‐ EE GEFS + phenotypes and de novo SCN 1A pathogenic variants, including a monozygotic twin pair. Febrile seizures plus ( FS +) occurred in six patients, five of whom had additional seizure types. The remaining case had childhood‐onset temporal lobe epilepsy without known febrile seizures. Although early development was normal in all individuals, three later had learning difficulties, and the twin girls had language impairment and working memory deficits. All cases had SCN 1A missense pathogenic variants that were not found in either parent. One pathogenic variant had been reported previously in a case of DS , and the remainder were novel. Our finding of de novo pathogenic variants in mild phenotypes within the GEFS + spectrum shows that mild GEFS + is not always inherited. SCN 1A screening should be considered in patients with GEFS + phenotypes because identification of pathogenic variants will influence antiepileptic therapy, and prognostic and genetic counseling.