Idiopathic mesial temporal lobe epilepsy: a syndrome with complex inheritance?

Abstract

In a recent article, Striano et al. [1] stated that familial mesial temporal lobe epilepsy was consistent with an autosomal dominant inheritance with incomplete penetrance. In fact, this pattern of inheritance was already proposed when the syndrome was recognized by Berkovic et al. [2]. Subsequently, others researchers extended the clinical spectrum of the disorder, but they still supported the same mode of genetic transmission [3, 4]. However, some observations could point against this general agreement. First, no very large pedigrees of familial mesial temporal lobe epilepsy have been reported to date [5]. In addition, 15 out of 39 pedigrees included in three of the referred series showed that all the affected members belonged to the proband’s generation [1–3], which would be unusual for an autosomal dominant inheritance. This would explain why only isolated families with different subtypes of the disorder have, so far, been mapped [6, 7]. On the other hand, the way in which the reported patients were ascertained could have caused a selection bias and, consequently, an inappropriate conclusion about the pattern of inheritance. Cases published in the four series cited above had to have one or more affected first-degree relatives to be included in the study [1–4]. This mode of recruitment determines that the families selected will automatically contain a high proportion of affected members [8]. However, there might be in the community other families with the same disorder, but with a single individual affected. The possibility that such families would be improperly excluded leads Ottmann to consider that the mode of inheritance of this syndrome is still uncertain [8]. Patients with sporadic presentation, but an otherwise similar phenotype to those with familial mesial temporal lobe epilepsy, have been described in the literature in several hospital series [9–12]. Compared to familial patients, these sporadic cases had identical seizure types, the same lack of acquired risk factors for epilepsy and a history of normal psychomotor development. Furthermore, the sporadic type was more prevalent than the familial one in these series. Although some of the previous observations could be explained by reduced penetrance of an autosomal dominant disorder, others would undoubtedly be more concordant with a disorder with complex inheritance. Until genetic studies support a different approach, it seems logical to include both sporadic and familial cases consistent with this syndrome under the name of ‘‘idiopathic mesial temporal lobe epilepsy’’ (IMTLE). As Berkovic et al. stated, twin studies allow an easy recognition of a genetic disorder even if the mode of inheritance is complex [2]. In fact, they initially identified familial mesial temporal lobe epilepsy in this manner. Later on, families that had a similar syndrome, collected from the private and hospital practice of one of the investigators, were added to this Australian series. As they admitted in their article, the twin families, taken from community-based registers, could be more representative of the general population than their nontwin families. However, after a segregation analysis, which included only their nontwin families, the authors concluded that the disorder was suggestive of an autosomal dominant inheritance with reduced penetrance. In their study, among five families of concordant monozygotic pairs, only one pedigree showed some other affected relatives, which led them to suggest that this genetic disorder could also be a frequent cause of apparently sporadic cases. Therefore, it could be reasonable to support the inclusion of all cases of the J. Gomez-Alonso (&) D. Munoz-Garcia M. Aguado Servicio de Neurologia, Hospital Xeral-Cies, Pizarro 22, 36204 Vigo, Spain e-mail: juan.gomez.alonso@sergas.es