Late onset epileptic spasms is frequent in MECP2 gene duplication: electroclinical features and long-term follow-up of 8 epilepsy patients

Mutation of the X-linked methyl CpG binding protein 2 (MECP2) has been first identified as the cause of Rett syndrome. More recently, MECP2 gene duplication syndrome has been identified in males. The MECP2 duplication syndrome is characterized by severe mental retardation, infantile hypotonia, progressive spasticity and recurrent infections. Epileptic seizures are inconstant but poorly described. The aim of the study is to describe the electroclinical features of epilepsy in MECP2 duplication patients in order to refine the epilepsy phenotype and its evolution.

Methods: We conducted a retrospective study in four child neurology departments in France. Eight boys with a MECP2 gene duplication and epilepsy were retrospectively studied. We evaluated both clinical and electroencephalographic data before seizure onset, at seizure onset and during the follow-up.

Results: The patients started seizures at the median age of 6 years (range: 2.5-17 years). Half exhibits late onset epileptic spasms while the other exhibit either focal epilepsy or unclassified generalized epilepsy. Before seizure onset, EEGs were abnormal in all patients showing a slowing of the background or a normal background with fast activities, while EEG performed in epileptic patients, showed a slowing of the background in 6/8 and localized slow or sharp waves in 7/8. Most patients (6/8) have evolved to drug resistant epilepsy.

Conclusion: Although late onset epileptic spasms are common in patients with MECP2 duplication, no specific electroclinical phenotype emerges, probably due to genetic heterogeneity of the syndrome. Further studies are needed to individualize specific epileptic subtype in larger cohort of patients.