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  • Updated 03.29.2021
  • Released 07.07.2004
  • Expires For CME 03.29.2024

Familial lateral temporal lobe epilepsy



Recognition of a genetic basis of temporal lobe epilepsy in some families represents a major advance. In familial forms of lateral temporal lobe epilepsy with auditory features, LGI1 or RELN genes are mutated in approximately 50% of kindreds. In this article, the author reports on a large cohort of patients with epilepsy and auditory features in which a third of 112 cases were familial, with an underlying genetic diagnosis in 8% of individuals, including LGI-1, RELN, SCNA1, and DEPDC5 mutations. Moreover, the author highlights that patients with familial lateral temporal lobe epilepsy with RELN mutations can present with drug-resistant seizures and be associated with structural and functional neuroimaging temporal lobe abnormalities.

Key points

• Familial lateral temporal lobe epilepsy is typically characterized by auditory auras, but other types of clinical manifestations can be present in affected individuals.

• Drug-resistant seizures and neuroimaging abnormalities might be present in some affected individuals.

• Mutations in LGI1, RELN, DEPDC5, and SCNA1 genes have been reported.

• Approximately 50% of families have a genetic diagnosis clarified, of which mutations in the LGI1 gene or RELN gene are the most frequent.

Historical note and terminology

Genetic factors in the causation of epilepsy have been recognized since the time of Hippocrates. However, until the second half of the 20th century, generalized epilepsies were thought to be genetic in origin, whereas focal epilepsies were largely attributed to environmental factors, such as birth injuries, infections, postnatal head trauma, and brain lesions such as tumors and vascular insults.

In a series of publications (05; 01; 02; 03) based on patients operated for focal epilepsy at the Montreal Neurological Hospital, Eva Andermann was able to demonstrate that genetic factors were important in patients with focal epilepsy, particularly temporal lobe epilepsy, and that both generalized and focal epilepsies fit a model of multifactorial inheritance (now termed complex inheritance), with interaction of 1 or more genes and environmental factors.

It was only in the 1990s that several autosomal dominant forms of focal epilepsy were described by the group of Berkovic and colleagues (12). These included: autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy, familial focal epilepsy with variable foci, and autosomal dominant rolandic epilepsy with speech dyspraxia.

Familial temporal lobe epilepsy was included in the proposals for classification of epileptic syndromes by the International League Against Epilepsy, supporting it as a well-defined syndrome (36; 35; 09).

The first description of familial lateral temporal lobe epilepsy was in 1995 by Ottman and colleagues, who reported an autosomal dominant focal epilepsy syndrome with auditory features (72). Autosomal dominant partial epilepsy syndrome with auditory features corresponds to a neocortical or lateral temporal lobe epilepsy.

After detailed descriptions of many families with temporal lobe epilepsy, it has been possible to define 2 groups of familial temporal lobe epilepsy based on clinical and molecular characteristics (91; 04): familial mesial temporal lobe epilepsy, with clinical features of mesial temporal onset and no clear-cut molecular definition to date (57; 54); and familial lateral temporal lobe epilepsy, first described in association with LGI1 gene mutations in chromosome 10q (72; 51; 70).

It is important to recognize that it is impossible to distinguish familial and nonfamilial temporal lobe epilepsy patients based solely on the clinical presentation, for both mesial and lateral forms. As the family history is not always accurately documented and because some family members are asymptomatic or only mildly affected, many so-called “sporadic” or “isolated” patients may actually have a familial epilepsy syndrome.

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