Spectrum and time course of epilepsy and the associated cognitive decline in MECP2 duplication syndrome

Neurology. 2019 Jan 8;92(2):e108-e114. doi: 10.1212/WNL.0000000000006742. Epub 2018 Dec 14.


Objective: We characterized the epilepsy features and contribution to cognitive regression in 47 patients with MECP2 duplication syndrome (MDS) and reviewed these characteristics in over 280 MDS published cases.

Methods: The institutional review board approved this retrospective review of medical records and case histories of patients with MDS.

Results: The average age at enrollment was 10 ± 7 years. Patients with epilepsy were older (13 ± 7 years vs 8 ± 5 years, p = 0.004) and followed for a longer time (11.8 ± 6.5 years vs 6.3 ± 4.2 years, p = 0.003) than patients without a seizure disorder. Epilepsy affected 22/47 (47%) patients with MDS. It was treatment-refractory and consistent with epileptic encephalopathy in 18/22 (82%) cases. Lennox-Gastaut syndrome (LGS) was present in 12/22 (55%) patients and manifested between late childhood and adulthood in 83% of cases. The emergence of neurologic regression coincided with the onset of epilepsy. The MECP2 duplication size and gene content did not correlate with epilepsy presence, type, age at onset, or treatment responsiveness.

Conclusion: Epilepsy in MDS is common, often severe, and medically refractory. LGS occurs frequently and may have a late onset. Developmental regression often follows the onset of epilepsy. The MECP2 duplication extent and gene content do not discriminate between patients with or without epilepsy. Our findings inform clinical care and family counseling with respect to early epilepsy recognition, diagnosis, specialty referral, and implementation of aggressive seizure therapy to minimize detrimental effect of uncontrolled seizures on cognitive functions or preexisting neurologic deficits.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cognition Disorders / diagnostic imaging
  • Cognition Disorders / etiology*
  • Cognition Disorders / genetics
  • Epilepsy / diagnostic imaging
  • Epilepsy / etiology*
  • Epilepsy / genetics
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Mental Retardation, X-Linked / complications*
  • Mental Retardation, X-Linked / diagnostic imaging
  • Mental Retardation, X-Linked / genetics
  • Retrospective Studies
  • Surveys and Questionnaires
  • Young Adult

Supplementary concepts

  • Lubs X-linked mental retardation syndrome