RT Journal Article SR Electronic T1 Phenotypic Spectrum of Seizure Disorders in MBD5-Associated Neurodevelopmental Disorder JF Neurology Genetics JO Neurol Genet FD Lippincott Williams & Wilkins SP e579 DO 10.1212/NXG.0000000000000579 VO 7 IS 2 A1 Myers, Kenneth A. A1 Marini, Carla A1 Carvill, Gemma L. A1 McTague, Amy A1 Panetta, Julie A1 Stutterd, Chloe A1 Stanley, Thorsten A1 Marin, Samantha A1 Nguyen, John A1 Barba, Carmen A1 Rosati, Anna A1 Scott, Richard H. A1 Mefford, Heather C. A1 Guerrini, Renzo A1 Scheffer, Ingrid E. YR 2021 UL http://ng.neurology.org/content/7/2/e579.abstract AB Objective To describe the phenotypic spectrum in patients with MBD5-associated neurodevelopmental disorder (MAND) and seizures; features of MAND include intellectual disability, epilepsy, psychiatric features of aggression and hyperactivity, and dysmorphic features including short stature and microcephaly, sleep disturbance, and ataxia.Methods We performed phenotyping on patients with MBD5 deletions, duplications, or point mutations and a history of seizures.Results Twenty-three patients with MAND and seizures were included. Median seizure onset age was 2.9 years (range 3 days–13 years). The most common seizure type was generalized tonic-clonic; focal, atypical absence, tonic, drop attacks, and myoclonic seizures occurred frequently. Seven children had convulsive status epilepticus and 3 nonconvulsive status epilepticus. Fever, viral illnesses, and hot weather provoked seizures. EEG studies in 17/21 patients were abnormal, typically showing slow generalized spike-wave and background slowing. Nine had drug-resistant epilepsy, although 3 eventually became seizure-free. All but one had moderate-to-severe developmental impairment. Epilepsy syndromes included Lennox-Gastaut syndrome, myoclonic-atonic epilepsy, and infantile spasms syndrome. Behavioral problems in 20/23 included aggression, self-injurious behavior, and sleep disturbance.Conclusions MBD5 disruption may be associated with severe early childhood-onset developmental and epileptic encephalopathy. Because neuropsychiatric dysfunction is common and severe, it should be an important focus of clinical management.DS=Dravet syndrome; FS+=febrile seizures plus; LGS=Lennox-Gastaut syndrome; MAE=myoclonic-atonic epilepsy; MAND=MBD5-associated neurodevelopmental disorder