Authors :
Presenting Author: Yew Li Dang, MB BCh BAO, FRACP – Epilepsy Research Centre, Department of Medicine (Austin Health), The University of Melbourne, Australia; Bladin-Berkovic Comprehensive Epilepsy Program, Austin Health, Melbourne, Australia
Kate Esnault, BSc (Hons) – Epilepsy Research Centre, Department of Medicine (Austin Health), The University of Melbourne, Melbourne, Australia; Piero Perucca, MD, PhD, FRACP – Epilepsy Research Centre, Department of Medicine (Austin Health), The University of Melbourne, Melbourne, Australia; Bladin-Berkovic Comprehensive Epilepsy Program, Austin Health, Melbourne, Australia; Samuel Berkovic, AM, MD, FAA, FRACP, FRS – (Epilepsy Research Centre, Department of Medicine (Austin Health), The University of Melbourne, Melbourne, Australia; Bladin-Berkovic Comprehensive Epilepsy Program, Austin Health, Melbourne, Australia
Rationale:
Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. TLE was historically regarded as a largely acquired disorder but has now been shown to have a genetic contribution. An improved understanding of the heritability and genetic architecture of TLE may provide important insights into the etiology of this common condition.
Methods:
Twin pairs with a history of seizures were ascertained from community-based twin registers and by referral from neurologists. Participants’ medical records were analyzed and a validated seizure questionnaire and clinical examination were completed. Diagnosis of TLE and sub-classification of mesial TLE (mTLE) were determined according to specified criteria. Twin pairs with imaging and/or histopathological findings of hippocampal sclerosis (HS) were classified as mTLE-HS. Casewise concordances were calculated and compared between monozygotic (MZ) and dizygotic (DZ) twins to determine the heritability for specific TLE syndromes.
Results: Sixty-five twin pairs (36 MZ, 29 DZ; Figure 1) were diagnosed with non-lesional TLE. 15/36 MZ twins were concordant for non-lesional TLE, with no concordant DZ twins observed (MZ casewise concordance P
MZ =0.59; DZ casewise concordance, P
DZ =0). Thirty-nine twin pairs fulfilled diagnostic criteria for mTLE, comprising of 24 MZ and 15 DZ twins. 14/24 MZ twin pairs were concordant for mTLE (P
MZ 0.74; P
DZ =0). 26/65 (12 MZ, 14 DZ) of the non-lesional TLE twin pairs had non-mesial TLE, with only one of the 12 MZ pairs concordant for non-mesial TLE (P
MZ =0.15; P
DZ =0).
15/39 (7 MZ, 8 DZ) twin pairs with mTLE had HS in at least one twin, with one concordant MZ twin pair and no concordant DZ pairs for mTLE-HS (P
MZ =0.25; P
DZ =0). In contrast to the low MZ concordance in the HS group, the remaining 24 twin pairs with mTLE without HS revealed a very high MZ casewise concordance (P
MZ =0.87; P
DZ =0).
Of the 14 concordant mTLE twin pairs, seven twin individuals had a co-twin who was not initially diagnosed with epilepsy. After detailed questioning, 6/7 had unrecognized focal aware seizures (FAS) consistent with mTLE semiology and 1/7 reported both focal impaired awareness seizures (FIAS) and FAS. In the remaining 7/14 concordant twin pairs with mTLE where both twins were diagnosed with epilepsy, 5/7 had focal to bilateral tonic-clonic seizures in addition to FAS and FIAS.
Conclusions:
This large cohort of twins with non-lesional TLE shows a higher concordance in MZ compared to DZ twins, an effect largely driven by the very high MZ concordance seen in mTLE twin pairs. This data provides further support for genetic factors having a major role in non-lesional mesial TLE and suggests that genetic contributions to non-mesial TLE and mTLE-HS may be smaller.
Funding:
National Health and Medical Research Council of Australia