Biallelic OTUD6B variants associated with a Kabuki syndrome-like disorder in three siblings: A clinical report and literature review

Am J Med Genet A. 2024 Jul;194(7):e63567. doi: 10.1002/ajmg.a.63567. Epub 2024 Feb 22.


Biallelic variants in the OTUD6B gene have been reported in the literature in association with an intellectual developmental disorder featuring dysmorphic facies, seizures, and distal limb abnormalities. Physical differences described for affected individuals suggest that the disorder may be clinically recognizable, but previous publications have reported an initial clinical suspicion for Kabuki syndrome (KS) in some affected individuals. Here, we report on three siblings with biallelic variants in OTUD6B co-segregating with neurodevelopmental delay, shared physical differences, and other clinical findings similar to those of previously reported individuals. However, clinical manifestations such as long palpebral fissures, prominent and cupped ears, developmental delay, growth deficiency, persistent fetal fingertip pads, vertebral anomaly, and seizures in the proband were initially suggestive of KS. In addition, previously unreported clinical manifestations such as delayed eruption of primary dentition, soft doughy skin with reduced sweating, and mirror movements present in our patients suggest an expansion of the phenotype, and we perform a literature review to update on current information related to OTUD6B and human gene-disease association.

Keywords: IDDFSDA; Kabuki syndrome; OTUD6B; developmental delay; microcephaly; seizures.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Abnormalities, Multiple* / genetics
  • Abnormalities, Multiple* / pathology
  • Alleles
  • Child
  • Child, Preschool
  • Endopeptidases / genetics
  • Face* / abnormalities
  • Face* / pathology
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Hematologic Diseases* / diagnosis
  • Hematologic Diseases* / genetics
  • Hematologic Diseases* / pathology
  • Humans
  • Intellectual Disability / genetics
  • Intellectual Disability / pathology
  • Male
  • Mutation / genetics
  • Neck / abnormalities
  • Neck / pathology
  • Phenotype*
  • Siblings*
  • Vestibular Diseases* / diagnosis
  • Vestibular Diseases* / genetics
  • Vestibular Diseases* / pathology


  • Endopeptidases
  • OTUD6B protein, human

Supplementary concepts

  • Kabuki syndrome