Consanguinity in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis in a Saudi population

Discussion

This retrospective case-control study was conducted at one of the epilepsy centers in Saudi Arabia, to determine if consanguinity is associated with HS in patients with TLE. The ratio of the number of individuals in the HS group to those in the control group in this study was 1:2. This study suggests that parental consanguinity might have a positive association with HS. A review on focal drug-resistant epilepsy by a Moroccan group found that mesial temporal lobe syndrome is associated with a high frequency of febrile convulsions and parental consanguinity.11 However, their cohort included only 6 patients with parental consanguinity. The association between consanguinity and epilepsy was also investigated by Babtain et al,2 who observed a lack of association between first-degree consanguinity and the risk of developing epilepsy, in the southern region of Saudi Arabia. However, in this study, second-degree consanguinity increased the risk of developing epilepsy. The social stigma of epilepsy possibly contributes to the observed lack of association between epilepsy and first-degree consanguinity. It seems that due to unfortunate social stigma experienced by patients with epilepsy, people with epilepsy avoid getting married to first-degree relatives, and they also think of avoiding the “transmit” of the disease to their children should they indulge.

Thus, a second-degree marriage is quite common, as an alternative to first-degree in Saudi Arabia and considered “ideal way” by many families to avoid having children with genetically inherited disease. It is well known that a family history of epilepsy is strongly associated with epilepsy, which was also noted in this study. Khan et al3 examined the association between parental consanguinity and family history with the risk of developing idiopathic epilepsy; 17% of the observed epilepsy cases were associated with a history of parental consanguinity, but consanguinity was also observed in 31% of the control group, which consists of non-epileptic cohort extracted randomly from the same hospital record. On the other hand, a family history of epilepsy was observed in 81% of the epilepsy cases, while it was found in only 17% of the controls. It is worthy of note that this study considered only 76 patients.3 It is also important to note that a family history of epilepsy seems to have a strong association with the risk of developing epilepsy in the 2 studies mentioned above. This observation was validated in this current study. In the same Saudi population, a relationship between parental consanguinity and presumed familial type of multiple sclerosis was reported by Jumah et al.12 Such findings and the ones from this study may contribute to the field by enhancing existing knowledge regarding the risk of developing such neurological disorders without known inheritance patterns or described association with parental consanguinity.

Our results suggested that consanguineous marriage could be a direct or indirect contributing factor in focal epilepsy due to HS.

Gambardella et al,13 reported 8 patients from Italy with autosomal dominant FMTLE, but with incomplete penetrance, all patients had controlled seizures on antiepileptic drugs. In another study on FMTLE, a benign pattern was also observed in patients with and without HS; the prevalence of refractory epilepsy in FMTLE is less than that in typical surgical MTLE. Moreover, varying degrees of HS was observed in asymptomatic family members of patients with FMTLE, suggesting that the hippocampal abnormalities could be inherited. The degree of HS severity on MRI alone was not directly related to seizure severity and the development of refractory epilepsy, which is rather due to the complexity of MTLE pathogenesis and its underlying multifactorial etiologies.10 These findings are replicated in other studies where detecting HS in MRI was found in many patients with benign MTLE.14,15 However, a recent prospective study on patients with mild MTLE associated with the presence of HS leads to the progression of benign to refractory MTLE that requires surgical intervention.16 Genetic etiology has been demonstrated by several types of focal epilepsy in adult patients. The genetic basis of autosomal dominant partial epilepsy with auditory features was described by Winawer et al.17 The predisposing gene is localized in the 10 cM regions on chromosome 10q24. Angelicheva et al18 examined the genetic basis of early-onset TLE syndrome in the Gypsy population. They identified an association between the syndrome and the loci 5q31.3-q32 and 10p12. These findings suggest that genetic susceptibility increases the likelihood of developing focal epilepsy. Our findings of linking consanguinity to HS, may emphasize the same notion. On the contrary, Striano et al19 reported clinical and genetic findings from 15 Italian families with FMTLE. The clinical and genetic findings were heterogeneous and could be linked to the studied loci or mutations.

We also observed an association between the history of FS and HS, found in 19.5% of the HS group and 11% of the control group. It is important to point out that sodium channel mutations lead to a homogenous phenotype of FS that is associated with HS. Colosimo et al20 and Scheffer et al21 recently demonstrated these mutations (SCN1A or SCN1B). Colosimo et al20 illustrated that out of 13 affected family members, 2 exhibited HS. Both cases showed focal complex or nocturnal secondary generalized tonic-clonic seizures. Scheffer et al21 performed SCN1B analysis on 402 individuals, only one of whom exhibited HS. This favors the hypothesis of a common genetic basis for TLE and FS, with or without HS.

In this study, we found that 65% of the patients who underwent anterior mesial temporal lobe resection had an excellent surgical outcome and became seizure-free after the surgery.22 The rate of seizure freedom is similar to what is reported in the literature for this type of epilepsy surgery.23,24