Broad neurodevelopmental features and cortical anomalies associated with a novel de novo KMT2A variant in Wiedemann-Steiner syndrome

Eur J Med Genet. 2021 Feb;64(2):104133. doi: 10.1016/j.ejmg.2020.104133. Epub 2020 Dec 30.


Wiedemann-Steiner syndrome (WDSTS) is a rare genetic disorder including developmental delay/intellectual disability (DD/ID), hypertrichosis cubiti, short stature, and distinctive facial features, caused by mutation in KMT2A gene, which encodes a histone methyltransferase (H3K4) that regulates chromatin-mediated transcription. Different neurodevelopmental phenotypes have been described within the WDSTS spectrum, including a peculiar Autism Spectrum Disorder (ASDs) subtype in some affected individuals. Here, we report a 9-year-old Caucasian male found by next-generation panel sequencing to carry a novel heterozygous de novo KMT2A frameshift variant (NM_001197104.2:c.4433delG; p. Arg1478LeufsTer108). This boy presented a WDSTS phenotype associated with broad neurodevelopmental features, including an unusual speech difficulty (i.e., palilalia), and brain imaging studies revealed an array of cortical anomalies (e.g., frontal simplified gyration, focal frontal cortical dysplasia). These clinical and radiological observations expand the known WDSTS-related neurodevelopmental phenotypes and further strengthen the important role of KMT2A in brain function and cortical development.

Keywords: Focal cortical dysplasia; Hypertrichosis cubiti; KMT2A; Palilalia; Wiedemann-steiner syndrome.

Publication types

  • Case Reports

MeSH terms

  • Cerebral Cortex / diagnostic imaging
  • Child
  • Developmental Disabilities / diagnostic imaging
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • Frameshift Mutation
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Intellectual Disability / diagnostic imaging
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Male
  • Malformations of Cortical Development / diagnostic imaging
  • Malformations of Cortical Development / genetics*
  • Malformations of Cortical Development / pathology
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Syndrome


  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase