Low penetrance of autosomal dominant lateral temporal epilepsy in Italian families withoutLGI1mutations

Abstract

A large number of ADLTE families has been collected over a 10-year period in Italy, showing a typical and homogeneous phenotype. LGI1 mutations have been found in only one third of families, clinically indistinguishable from nonmutated pedigrees. The estimate of penetrance and OR, however, demonstrates a significantly lower penetrance rate and relative disease risk in non-LGI1-mutated families compared with LGI1-mutated pedigrees, suggesting that a complex inheritance pattern may underlie a proportion of these families.

Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

“…Mutations associated with ADLTE are found in leucine-rich, glioma inactivated 1 (LGI1 [MIM: 604619]) 4-6 in 30%-50% of ADLTE-affected families. 3,7,8 Other genes harboring ADLTE-causing mutations are unknown.LGI1 is expressed mainly in neurons, particularly in the neocortex and limbic regions, 4,9 and its protein product, LGI1, is secreted. 9 LGI1 has been implicated in the transmission of K þ and AMPA synaptic currents 10,11 and in the regulation of post-natal maturation of cortical excitatory synapses and dendrite pruning.…”

“…Mutations associated with ADLTE are found in leucine-rich, glioma inactivated 1 (LGI1 [MIM: 604619]) [4][5][6] in 30%-50% of ADLTE-affected families. 3,7,8 Other genes harboring ADLTE-causing mutations are unknown.…”

“…Most of these families have been described previously. 7 We reassessed the epilepsy phenotypes of affected members to confirm eligibility for linkage analysis on the basis of clinical features and intrafamilial clinical homogeneity. Each family contained two or more affected individuals with a history of focal epilepsy with auras characteristic of the syndrome, i.e., auditory (ringing, humming, sounds, voices, or music) and/or receptiveaphasic symptoms, and absence of identified structural or metabolic insults to the CNS.…”

Seizures and Epilepsies due to Channelopathies and Neurotransmitter Receptor Dysfunction: A Parallel between Genetic and Immune Aspects

“…The prevalence of this affection is currently unknown, with dozens of families reported, particularly in Italy [Michelucci et al, 2013]. The age of onset is variable ranging from 8 to 50 years [Michelucci et al, 2003] but usually emerging in adolescence and early childhood [Ho et al, 2012].…”

Comments from the Editor(s)

“…3 Although the diagnosis of FMTLE could be reconsidered based on this new finding, this kindred cannot be classified as ADLTE because ADLTE families must comprise at least two affected members with a history of focal epilepsy with auditory or aphasic symptoms. 4,5 Families with recurrent epilepsy in which a single affected member has auditory auras likely belong to a heterogeneous clinical/genetic entity including multiple types of familial epilepsies. It is not unlikely that a proportion of these families, especially the small ones, may actually have clear-cut autosomal dominant epilepsy syndromes, which remain unrecognized owing to small family size.…”