PT  - JOURNAL ARTICLE
AU  - Myers, Kenneth A.
AU  - Marini, Carla
AU  - Carvill, Gemma L.
AU  - McTague, Amy
AU  - Panetta, Julie
AU  - Stutterd, Chloe
AU  - Stanley, Thorsten
AU  - Marin, Samantha
AU  - Nguyen, John
AU  - Barba, Carmen
AU  - Rosati, Anna
AU  - Scott, Richard H.
AU  - Mefford, Heather C.
AU  - Guerrini, Renzo
AU  - Scheffer, Ingrid E.
TI  - Phenotypic Spectrum of Seizure Disorders in MBD5-Associated Neurodevelopmental Disorder
AID  - 10.1212/NXG.0000000000000579
DP  - 2021 Apr 01
TA  - Neurology Genetics
PG  - e579
VI  - 7
IP  - 2
4099  - http://ng.neurology.org/content/7/2/e579.short
4100  - http://ng.neurology.org/content/7/2/e579.full
SO  - Neurol Genet2021 Apr 01; 7
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