Long term outcome of patients with Epilepsy with migrating focal seizure in infancy (EMFSI) due to KCNT1 mutation

Abstract

Introduction: MMPSI or EMFSI was described in 1995. KCNT1 is the major gene causing this rare epilepsy with other causative genes recently reported. However, little is known about the outcome of this syndrome mainly in term of long-term outcome. Methods: We studied medical data of patients with EMFSI due to KCNT1 mutation born before 2013. We completed medical data with a survey sent to the families on the status of their children over the last 6 months. Results: 12 patients were included (sex ratio: 1.4) and one patient was lost to follow-up. All families replied to the questionnaire. Fifty percent were deceased at the time of this study (n=6): 2 during the active epileptic phase in infancy at 0.3 and 1.5 y, 2 from SUDEP at 1.5 and 3 y and 2 from respiratory failure at 15 and 19.5 y after frequent respiratory infections. The other 6 were aged from 3.5 to 16 y (mean 10 ± 5 y). All patients had acquired microcephaly (−4.5 ± 2 SD) and a severe intellectual disability with major hypotonia. None acquired sitting position or language. Four patients were able to hold their head up. Only one patient could hold objects. Patients had eye contact and were able to communicate with their parents by modulating their vocals and crying and one was able to repeat “mama”. Seizures remain very frequent from at least one to 25 seizures a day and occurred in clusters (n=5). Parents describe seizures as hypertonic with a cry, extension of members and facial rictus. Main triggering factors were stress, emotion and pain. For five patients seizures were predominant during night time with no prodromal signs or trigger factors. Conclusion: MPSI is probably one of the most severe epileptic encephalopathies with severe intellectual and motor outcome and persistent active epilepsy.