Defining the phenotypic spectrum of SLC6A1 mutations

• DOI: 10.1111/epi.13986
• Publication Date: 2018-01-10T05:54:07Z
• Authors: Katrine M. Johann...; Elena Gardella; Tarja Linnankivi; Carolina Courage; Anne de Saint Martin; Anna‐Elina Lehesjoki; Cyril Mignot; Alexandra Afenjar; Gaetan Lesca; Marie‐Thérèse Abi...; Jamel Chelly; Amélie Piton; J. Lawrence Merritt; Lance H. Rodan; Wen‐Hann Tan; Lynne M. Bird; Mark Nespeca; Joseph G. Gleeson; Yongjin Yoo; Murim Choi; Jong‐Hee Chae; Desiree Czapansky...; Sara Chadwick Rei...; Manuela Pendziwiat; Judith S. Verhoeven; Helenius J. Schel...; Orrin Devinsky; Jakob Christensen; Nicola Specchio; Marina Trivisano; Yvonne G. Weber; Caroline Nava; Boris Keren; Diane Doummar; Elise Schaefer; Sarah Hopkins; Holly Dubbs; Jessica E. Shaw; Laura Pisani; Candace T. Myers; Sha Tang; Shan Tang; Deb K. Pal; John J. Millichap; Gemma L. Carvill; Kathrine L. Helbig; Oriano Mecarelli; Pasquale Striano; Ingo Helbig; Guido Rubboli; Heather C. Mefford; Rikke S. Møller
• Keywords: Valproic Acid; Seizure types; Proband; Generalized epilepsy; Epilepsy syndromes

Summary 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 a larger cohort of SCL6A1 ‐mutated patients. Methods collected 24 probands 6 affected family members. Four previously published cases included for further electroclinical description. In total, we reviewed data 34 subjects. Results Cognitive development was impaired 33/34 (97%) subjects; 28/34 had mild moderate ID, language impairment being most common feature. Epilepsy diagnosed 31/34 mean onset at 3.7 years. assessment before available 24/31 subjects normal 25% (6/24), consistent ID 46% (11/24) or 17% (4/24). Two speech delay only, 1 severe ID. After onset, cognition deteriorated cases. The seizure types absence, myoclonic, seizures. Sixteen fulfilled diagnostic criteria MAE. Seven different forms generalized 2 focal epilepsy. Twenty 31 became seizure‐free, valproic acid effective drug. There no clear‐cut correlation between control cognitive outcome. Electroencephalography (EEG) findings 27/31 showing irregular bursts diffuse 2.5‐3.5 Hz spikes/polyspikes‐and‐slow waves 25/31. developed an EEG pattern resembling electrical status epilepticus during sleep. Ataxia observed 7/34 describe 7 truncating 18 missense variants, including 4 recurrent (Gly232Val, Ala288Val, Val342Met, Gly362Arg). Significance Most carrying pathogenic have MAE phenotype mild/moderate onset. However, alone associated can also be observed.