, Volume 14, Issue 2, pp 99–111 | Cite as

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

  • Alex R. PaciorkowskiEmail author
  • 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. Ballif
  • Eric D. Marsh
Original Article


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.


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



We wish to thank the families of the subjects for sharing the details of their children’s condition with us. We recognize Natasha Vedage and Molly Bourke for their assistance with the immunohistochemistry, Erin Dodge for assistance with figure design, and Hailly Butler for assistance with subject consents.


WBD is funded by NINDS R01 NS058721; JAR and RAS are employees of Signature Genomic Laboratories, PerkinElmer; ANL is an employee of ARUP Laboratories; and RJV is an employee of Lineagen, Inc. The other authors have no disclosures.

Supplementary material

10048_2013_356_MOESM1_ESM.doc (96 kb)
ESM 1 (DOC 96 kb)
10048_2013_356_MOESM2_ESM.mpg (7.5 mb)
Video 1 Subject LR11-325 at 5 months, showing paroxysms of hyperkinetic movements of the arms and legs. These were not associated with epileptiform discharges on EEG. (MPG 7636 kb)
Video 2

Subject IS09-024 at 12 years, showing stereotypic hyperkinetic movements of the distal upper extremities. (AVI 6156 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Alex R. Paciorkowski
    • 1
    Email author
  • Ryan N. Traylor
    • 2
  • Jill A. Rosenfeld
    • 2
  • Jacqueline M. Hoover
    • 3
  • Catharine J. Harris
    • 4
  • Susan Winter
    • 5
  • Yves Lacassie
    • 6
  • Martin Bialer
    • 7
  • Allen N. Lamb
    • 8
  • Roger A. Schultz
    • 2
  • Elizabeth Berry-Kravis
    • 9
  • Brenda E. Porter
    • 10
  • Marni Falk
    • 11
  • Anu Venkat
    • 12
  • Rena J. Vanzo
    • 13
  • Julie S. Cohen
    • 14
  • Ali Fatemi
    • 14
  • William B. Dobyns
    • 15
  • Lisa G. Shaffer
    • 2
    • 16
  • Blake C. Ballif
    • 2
    • 16
  • Eric D. Marsh
    • 12
  1. 1.Departments of Neurology, Pediatrics, and Biomedical Genetics, Center for Neural Development & DiseaseUniversity of Rochester Medical CenterRochesterUSA
  2. 2.Signature Genomic Laboratories, PerkinElmer, Inc.SpokaneUSA
  3. 3.Department of Medical GeneticsChildren’s Hospital of PittsburghPittsburghUSA
  4. 4.Division of Medical Genetics, Department of Child HealthUniversity of MissouriColumbiaUSA
  5. 5.Department of Medical Genetics/MetabolismChildren’s Hospital of Central CaliforniaMaderaUSA
  6. 6.Department of PediatricsLouisiana State University Health Sciences Center, New Orleans, LA and Children’s HospitalNew OrleansUSA
  7. 7.Division of Medical GeneticsNorth Shore Long Island Jewish Health SystemNew Hyde ParkUSA
  8. 8.ARUP LaboratoriesUniversity of UtahSalt Lake CityUSA
  9. 9.Departments of Pediatrics, Neurological Sciences & BiochemistryRush University Medical CenterChicagoUSA
  10. 10.Department of NeurologyStanford UniversityStanfordUSA
  11. 11.Department of Medical GeneticsChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  12. 12.Department of NeurologyChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  13. 13.Lineagen, Inc.Salt Lake CityUSA
  14. 14.Division of Neurogenetics, Kennedy Krieger InstituteJohns Hopkins Medical InstitutionsBaltibmoreUSA
  15. 15.Division of Genetic Medicine, Department of PediatricsUniversity of Washington and Seattle Children’s Research InstituteSeattleUSA
  16. 16.Paw Print Genetics, Genetic Veterinary Sciences, Inc.SpokaneUSA

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