Defining the phenotypic spectrum of SLC6A1 mutations
- Creators
- Johannesen K. M.
- Gardella E.
- Linnankivi T.
- Courage C.
- de Saint Martin A.
- Lehesjoki A. -E.
- Mignot C.
- Afenjar A.
- Lesca G.
- Abi-Warde M. -T.
- Chelly J.
- Piton A.
- Merritt J. L.
- Rodan L. H.
- Tan W. -H.
- Bird L. M.
- Nespeca M.
- Gleeson J. G.
- Yoo Y.
- Choi M.
- Chae J. -H.
- Czapansky-Beilman D.
- Reichert S. C.
- Pendziwiat M.
- Verhoeven J. S.
- Schelhaas H. J.
- Devinsky O.
- Christensen J.
- Specchio N.
- Trivisano M.
- Weber Y. G.
- Nava C.
- Keren B.
- Doummar D.
- Schaefer E.
- Hopkins S.
- Dubbs H.
- Shaw J. E.
- Pisani L.
- Myers C. T.
- Tang S.
- Tang S.
- Pal D. K.
- Millichap J. J.
- Carvill G. L.
- Helbig K. L.
- Mecarelli O.
- Striano P.
- Helbig I.
- Rubboli G.
- Mefford H. C.
- Moller R. S.
- Others:
- Johannesen, K. M.
- Gardella, E.
- Linnankivi, T.
- Courage, C.
- de Saint Martin, A.
- Lehesjoki, A. -E.
- Mignot, C.
- Afenjar, A.
- Lesca, G.
- Abi-Warde, M. -T.
- Chelly, J.
- Piton, A.
- Merritt, J. L.
- Rodan, L. H.
- Tan, W. -H.
- Bird, L. M.
- Nespeca, M.
- Gleeson, J. G.
- Yoo, Y.
- Choi, M.
- Chae, J. -H.
- Czapansky-Beilman, D.
- Reichert, S. C.
- Pendziwiat, M.
- Verhoeven, J. S.
- Schelhaas, H. J.
- Devinsky, O.
- Christensen, J.
- Specchio, N.
- Trivisano, M.
- Weber, Y. G.
- Nava, C.
- Keren, B.
- Doummar, D.
- Schaefer, E.
- Hopkins, S.
- Dubbs, H.
- Shaw, J. E.
- Pisani, L.
- Myers, C. T.
- Tang, S.
- Tang, S.
- Pal, D. K.
- Millichap, J. J.
- Carvill, G. L.
- Helbig, K. L.
- Mecarelli, O.
- Striano, P.
- Helbig, I.
- Rubboli, G.
- Mefford, H. C.
- Moller, R. S.
Description
Objective: Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1-mutated patients. Methods: We collected 24 SLC6A1 probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects. Results: Cognitive development was impaired in 33/34 (97%) subjects; 28/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31/34 cases with mean onset at 3.7 years. Cognitive assessment before epilepsy onset was available in 24/31 subjects and was normal in 25% (6/24), and consistent with mild ID in 46% (11/24) or moderate ID in 17% (4/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11/24) of cases. The most common seizure types were absence, myoclonic, and atonic seizures. Sixteen cases fulfilled the diagnostic criteria for MAE. Seven further patients had different forms of generalized epilepsy and 2 had focal epilepsy. Twenty of 31 patients became seizure-free, with valproic acid being the most effective drug. There was no clear-cut correlation between seizure control and cognitive outcome. Electroencephalography (EEG) findings were available in 27/31 patients showing irregular bursts of diffuse 2.5-3.5 Hz spikes/polyspikes-and-slow waves in 25/31. Two patients developed an EEG pattern resembling electrical status epilepticus during sleep. Ataxia was observed in 7/34 cases. We describe 7 truncating and 18 missense variants, including 4 recurrent variants (Gly232Val, Ala288Val, Val342Met, and Gly362Arg). Significance: Most patients carrying pathogenic SLC6A1 variants have an MAE phenotype with language delay and mild/moderate ID before epilepsy onset. However, ID alone or associated with focal epilepsy can also be observed.
Additional details
- URL
- http://hdl.handle.net/11567/1022019
- URN
- urn:oai:iris.unige.it:11567/1022019
- Origin repository
- UNIGE