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