Further delineation and long-term evolution of electroclinical phenotype in Mowat Wilson Syndrome. A longitudinal study in 40 individuals

Abstract

BACKGROUND\nEpilepsy is a main feature of Mowat Wilson Syndrome (MWS), a congenital malformation syndrome caused by ZEB2 variants. The aim of this study was to investigate the long-term evolution of the electroclinical phenotype of MWS in a large population.\n\n\nMETHODS\nForty-individuals with a genetically confirmed diagnosis were enrolled. Three age groups were identified (t1\u202f=\u202f0-4; t2\u202f=\u202f5-12; t3\u202f=\u202f>13\u202fyears); clinical data and EEG records were collected, analyzed, and compared for age group. Video-EEG recorded seizures were reviewed.\n\n\nRESULTS\nThirty-six of 40 individuals had epilepsy, of whom 35/35 aged >5\u202fyears. Almost all (35/36) presented focal seizures at onset (mean age at onset 3.4\u202f±\u202f2.3 SD) that persisted, reduced in frequency, in 7/22 individuals after the age of 13. Absences occurred in 22/36 (mean age at onset 7.2\u202f±\u202f0.9 SD); no one had absences before 6 and over 16\u202fyears old. Paroxysmal interictal abnormalities in sleep also followed an age-dependent evolution with a significant increase in frequency at school age (p\u202f=\u202f0.002) and a reduction during adolescence (p\u202f=\u202f0.008). Electrical Status Epilepticus during Sleep occurred in 14/36 (13/14 aged 5-13\u202fyears old at onset). Seven focal seizure ictal video-EEGs were collected: all were long-lasting and more visible clinical signs were often preceded by prolonged electrical and/or subtle (erratic head and eye orientation) seizures. Valproic acid was confirmed as the most widely used and effective drug, followed by levetiracetam.\n\n\nCONCLUSIONS\nEpilepsy is a major sign of MWS with a characteristic, age-dependent, electroclinical pattern. Improvement with adolescence/adulthood is usually observed. Our data strengthen the hypothesis of a GABAergic transmission imbalance underlying ZEB2-related epilepsy.