MED13L haploinsufficiency syndrome: A de novo frameshift and recurrent intragenic deletions due to parental mosaicism

Am J Med Genet A. 2017 May;173(5):1264-1269. doi: 10.1002/ajmg.a.38168. Epub 2017 Mar 29.


MED13L haploinsufficiency syndrome is a clinical condition manifesting intellectual disability and developmental delay in association with various complications including congenital heart defects and dysmorphic features. Most of the previously reported patients showed de novo loss-of-function mutations in MED13L. Additional three patients with MED13L haploinsufficiency syndrome were identified here in association with rare complications. One patient had a de novo deletion (c.257delT) and T2-weighted high intensity in the occipital white matter on magnetic resonance imaging. Two siblings exhibited an intragenic deletion involving exons 3-14, which led to an in-frame deletion in MED13L. The deletion was inherited from their carrier mother who possessed low frequency mosaicism. The older sister of the siblings showed craniosynostosis; this condition has never been reported in patients with MED13L haploinsufficiency syndrome. Dysmorphic features were observed in these patients; however, most of the findings were nonspecific. Further information would be necessary to understand this clinical condition better.

Keywords: MED13L haploinsufficiency syndrome; craniosynostosis; intellectual disability; loss-of-function; mosaic.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / physiopathology
  • Female
  • Frameshift Mutation
  • Haploinsufficiency / genetics
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / physiopathology
  • Humans
  • Infant
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Mediator Complex / genetics*
  • Mosaicism
  • Sequence Deletion
  • Siblings


  • MED13L protein, human
  • Mediator Complex