Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature

Int J Mol Sci. 2017 Dec 28;19(1):82. doi: 10.3390/ijms19010082.


Kabuki syndrome (KS) is a rare disorder characterized by multiple congenital anomalies and variable intellectual disability caused by mutations in KMT2D/MLL2 and KDM6A/UTX, two interacting chromatin modifier responsible respectively for 56-75% and 5-8% of the cases. To date, three KS patients with mosaic KMT2D deletions in blood lymphocytes have been described. We report on three additional subjects displaying KMT2D gene mosaics including one in which a single nucleotide change results in a new frameshift mutation (p.L1199HfsX7), and two with already-known nonsense mutations (p.R4484X and p.R5021X). Consistent with previously published cases, mosaic KMT2D mutations may result in mild KS facial dysmorphisms and clinical and neurobehavioral features, suggesting that these characteristics could represent the handles for genetic testing of individuals with slight KS-like traits.

Keywords: KMT2D/MLL2; developmental delay; kabuki syndrome; mosaicism.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / metabolism
  • Abnormalities, Multiple / physiopathology
  • Adolescent
  • Base Sequence
  • Child
  • Codon, Nonsense*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Face / abnormalities*
  • Face / physiopathology
  • Female
  • Frameshift Mutation*
  • Gene Expression
  • Hematologic Diseases / diagnosis
  • Hematologic Diseases / genetics*
  • Hematologic Diseases / metabolism
  • Hematologic Diseases / physiopathology
  • Humans
  • Mosaicism*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neuropsychological Tests
  • Vestibular Diseases / diagnosis
  • Vestibular Diseases / genetics*
  • Vestibular Diseases / metabolism
  • Vestibular Diseases / physiopathology


  • Codon, Nonsense
  • DNA-Binding Proteins
  • KMT2D protein, human
  • Neoplasm Proteins

Supplementary concepts

  • Kabuki syndrome