Autosomal dominant epilepsy with auditory features: a new LGI1 family including a phenocopy with cortical dysplasia

Karl Martin Klein, Manuela Pendziwiat, Rony Cohen, Silke Appenzeller, Carolien G.F. de Kovel, Felix Rosenow, Bobby P.C. Koeleman, Gregor Kuhlenbäumer, Liron Sheintuch, Ronel Veksler, Alon Friedman, Zaid Afawi, Ingo Helbig

Research output: Contribution to journalArticlepeer-review

Abstract

We report a new family with autosomal dominant epilepsy with auditory features (ADEAF) including focal cortical dysplasia (FCD) in the proband. We aim to identify the molecular cause in this family and clarify the relationship between FCD and ADEAF. A large Iranian Jewish family including 14 individuals with epileptic seizures was phenotyped including high-resolution 3-T MRI. We performed linkage analysis and exome sequencing. LGI1, KANK1 and RELN were Sanger sequenced. Seizure semiology of 11 individuals was consistent with ADEAF. The proband underwent surgery for right mesiotemporal FCD. 3-T MRIs in four individuals were unremarkable. Linkage analysis revealed peaks on chromosome 9p24 (LOD 2.43) and 10q22–25 (LOD 2.04). A novel heterozygous LGI1 mutation was identified in all affected individuals except for the proband indicating a phenocopy. Exome sequencing did not reveal variants within the chromosome 9p24 region. Closely located variants in KANK1 and a RELN variant did not segregate with the phenotype. We provide detailed description of the phenotypic spectrum within a large ADEAF family with a novel LGI1 mutation that was conspicuously absent in the proband with FCD, demonstrating that despite identical clinical symptoms, phenocopies in ADEAF families may exist. This family illustrates that rare epilepsy syndromes within a single family can have both genetic and structural etiologies.

Original languageEnglish
Pages (from-to)11-16
Number of pages6
JournalJournal of Neurology
Volume263
Issue number1
DOIs
StatePublished - 1 Jan 2016

Keywords

  • Autosomal dominant epilepsy with auditory features
  • Autosomal dominant lateral temporal lobe epilepsy
  • Autosomal dominant partial epilepsy with auditory features
  • Epilepsies, partial [C10.228.140.490.360]
  • Genetic research [C10.228.140.490.360]
  • LGI1 protein, human [T329500]

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