Ophthalmic manifestations in Kabuki (make-up) syndrome: A single-center pediatric cohort and systematic review of the literature

Eur J Med Genet. 2021 Jun;64(6):104210. doi: 10.1016/j.ejmg.2021.104210. Epub 2021 Mar 30.


Kabuki syndrome (KS) is a genetic disorder caused by pathogenic variants in KMT2D or KDM6A, and manifesting with multi-systemic involvement, including recognizable facial features, developmental delay and multiple congenital anomalies. Ophthalmological involvement has been described in varying rates in several studies. We aimed to evaluate the prevalence and nature of ophthalmological findings in a cohort of KS patients in Israel. Medical records of all patients diagnosed with KS in our tertiary center between 2004 and 2020 were retrospectively reviewed. Data collected included physical examination findings, molecular analysis as well as comprehensive ophthalmic characteristics including visual acuity, ocular alignment and motility, ocular adnexa, anterior segments and dilated fundus exams. Finally, an updated systematic review of the literature was performed. Thirteen unrelated patients were included in the study, diagnosed at an age raging from the first months of life to 20 years. Of these, three (23%) showed significant ophthalmological abnormalities, beyond the characteristic structural findings of long palpebral fissures and lower eyelid eversion. These included bilateral posterior colobomata in the first patient; bilateral ptosis, hypermetropia, esotropia, blue sclera and anisocoria in the second; and bilateral congenital cataracts in the third. To conclude, our findings underscore the importance of a comprehensive ophthalmological evaluation as part of the routine multidisciplinary assessment of children suspected/diagnosed with KS.

Keywords: Cataract; Coloboma; Kabuki syndrome; Ophthalmological findings.

Publication types

  • Case Reports
  • Systematic Review

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / pathology*
  • Adolescent
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / genetics
  • Eye Abnormalities / genetics
  • Eye Abnormalities / pathology*
  • Face / abnormalities*
  • Face / pathology
  • Hematologic Diseases / genetics
  • Hematologic Diseases / pathology*
  • Histone Demethylases / genetics
  • Humans
  • Infant
  • Neoplasm Proteins / genetics
  • Vestibular Diseases / genetics
  • Vestibular Diseases / pathology*
  • Visual Acuity


  • DNA-Binding Proteins
  • KMT2D protein, human
  • Neoplasm Proteins
  • Histone Demethylases
  • KDM6A protein, human

Supplementary concepts

  • Kabuki syndrome