Phenotypic spectrum of seizure disorders in MBD5-associated neurodevelopmental disorder

Kenneth A. Myers*, Carla Marini, Gemma L. Carvill, Amy McTague, Julie Panetta, Chloe Stutterd, Thorsten Stanley, Samantha Marin, John Nguyen, Carmen Barba, Anna Rosati, Richard H. Scott, Heather C. Mefford, Renzo Guerrini, Ingrid E. Scheffer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Article numbere579
JournalNeurology: Genetics
Issue number2
StatePublished - Apr 2021

ASJC Scopus subject areas

  • Clinical Neurology
  • Genetics(clinical)


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