Abstracts

Rationale:
MBD5-associated neurodevelopmental syndrome (MAND) is a genetic syndrome with features including intellectual disability, epilepsy, psychiatric features of aggression and hyperactivity, dysmorphic features including short stature and microcephaly, sleep disturbance and ataxia. Although seizures occur in over 80% of patients, the epileptology has not been clearly defined. We aimed to describe the spectrum of epilepsy phenotypes in MAND.
Method:
We performed epilepsy and developmental phenotyping on patients with MBD5 deletions, duplications or point mutations. Cases were ascertained clinically and through social media family support groups.
Results:
Our cohort of 23 patients had a median age of seizure onset of 2.9 years (range 3 days to 13 years). The most common seizure type was generalized tonic-clonic, though focal, atypical absence, tonic, drop attacks and myoclonic seizures also occurred frequently. Seven children had convulsive status epilepticus and three non-convulsive status epilepticus. One patient had infantile spasms and hypsarrhythmia. Fever, viral illnesses, and hot weather provoked seizures.  Of those with available EEG results, 17/21 were abnormal, typically showing generalized slow spike-wave and background slowing. Nine had refractory seizures, though three of these eventually became seizure-free. All but one had moderate to severe developmental impairment with language usually disproportionately affected. Epilepsy syndromes included Lennox-Gastaut syndrome, myoclonic-atonic epilepsy, and West syndrome. Behavioural abnormalities including aggression and self-injurious behaviour, and sleep disturbance occurred in 20/23.
Conclusion:
MBD5 disruption is frequently associated with severe early childhood-onset developmental and epileptic encephalopathy. Severe psychiatric dysfunction frequently occurs and should be an important focus of clinical management.
Funding:
:National Health and Medical Research Council, Research Institute of the McGill University Health Centre.