MEF2C Haploinsufficiency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways

Alex R. Paciorkowski, Ryan N. Traylor, Jill A. Rosenfeld, Jacqueline M. Hoover, Catharine J. Harris, Susan Winter, Yves Lacassie, Martin Bialer, Allen N. Lamb, Roger A. Schultz, Elizabeth Berry-Kravis, Brenda E. Porter, Marni Falk, Anu Venkat, Rena J. Vanzo, Julie S. Cohen, Ali Fatemi, William B. Dobyns, Lisa G. Shaffer, Blake C. BallifEric D. Marsh

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

MEF2C haploinsufficiency syndrome is an emerging neurodevelopmental disorder associated with intellectual disability, autistic features, epilepsy, and abnormal movements. We report 16 new patients with MEF2C haploinsufficiency, including the oldest reported patient with MEF2C deletion at 5q14.3. We detail the neurobehavioral phenotype, epilepsy, and abnormal movements, and compare our subjects with those previously reported in the literature. We also investigate Mef2c expression in the developing mouse forebrain. A spectrum of neurofunctional deficits emerges, with hyperkinesis a consistent finding. Epilepsy varied from absent to severe, and included intractable myoclonic seizures and infantile spasms. Subjects with partial MEF2C deletion were statistically less likely to have epilepsy. Finally, we confirm that Mef2c is present both in dorsal primary neuroblasts and ventral gamma-aminobutyric acid(GABA)ergic interneurons in the forebrain of the developing mouse. Given interactions with several key neurodevelopmental genes such as ARX, FMR1, MECP2, and TBR1, it appears that MEF2C plays a role in several developmental stages of both dorsal and ventral neuronal cell types.

Original languageEnglish (US)
Pages (from-to)99-111
Number of pages13
JournalNeurogenetics
Volume14
Issue number2
DOIs
StatePublished - May 2013
Externally publishedYes

Keywords

  • Autism
  • Deletion 5q14.3
  • Hyperkinesis
  • Infant-onset myoclonic epilepsy
  • Infantile spasms
  • Intellectual disability
  • MEF2C haploinsufficiency

Fingerprint Dive into the research topics of 'MEF2C Haploinsufficiency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways'. Together they form a unique fingerprint.

Cite this