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  • Updated 08.07.2023
  • Released 07.07.2004
  • Expires For CME 08.07.2026

Familial mesial temporal lobe epilepsy



In this update, the author reports on molecular studies of surgical specimens from patients with drug-resistant familial mesial temporal lobe epilepsy.

Key points

• Familial mesial temporal lobe epilepsy cannot be distinguished from nonfamilial cases on the basis of clinical, EEG, or MRI findings.

• Some families have a benign outcome, whereas others have a more heterogeneous presentation, including refractory patients.

• Hippocampal atrophy is a common feature in some families, not always associated with poor seizure control.

• No specific genes have been established for this syndrome thus far, although linkage to different loci and mutation in the DEPDC5 gene were described in individual families.

• Prevalence of familial mesial temporal lobe epilepsy is estimated at 20% to 24% of families with nonacquired focal epilepsy.

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 (08; 04; 05; 06) based on family studies of 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 one 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 Steinlein (19). 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.

The first description of familial occurrence of temporal lobe epilepsy was in 1994 by Berkovic and colleagues who described familial temporal lobe epilepsy as a benign syndrome with late seizure onset, no history of prolonged febrile seizures, and no MRI evidence for mesial temporal sclerosis (15). However, subsequent familial temporal lobe epilepsy series identified patients who were not as benign, with a high proportion of hippocampal atrophy, some of whom required surgical treatment for their epilepsy (24; 59). These families showed intrafamilial and interfamilial phenotypic heterogeneity with respect to history of prolonged febrile seizures, severity of the epilepsy and presence of hippocampal atrophy. The original series of Berkovic and colleagues (15; 17) was population-based, arising from a twin study, whereas the later publications were hospital-based.

Familial temporal lobe epilepsy was included in the proposal for classification of epileptic syndromes by the International League Against Epilepsy (ILAE), supporting it as a well-defined syndrome (35; 34). It has been further maintained in the 2010 ILAE commission report as an adolescence-adulthood electroclinical syndrome (14).

With the description of the lateral form of familial temporal lobe epilepsy, also known as autosomal dominant epilepsy with auditory features (72) and associated with mutations in the LGI-1 gene on chromosome 10q (50; 70), the distinction between mesial and lateral families became more obvious (19; 59; 60; 54; 77; 92; 16; 09).

It is important to recognize that it is impossible to distinguish between patients with familial and nonfamilial temporal lobe epilepsy 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 very mildly affected, many so-called “sporadic” or “isolated” patients may actually have a familial epilepsy syndrome.

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