Genetic Disorders Clinical Update: Coloboma


A coloboma (from the Greek word koloboma meaning curtailed or mutilated) describes a congenital abnormality most commonly resulting from a failure of the embryonic fissue to close during the 5th to 7th week of fetal life. The ocular malformation refers to a gap or hole in ocular tissue; structures that may be affected include the eyelids, cornea, iris, ciliary body, lens, optic nerve, retina and choroid. They may be unilateral, bilateral, an isolated finding or part of a genetic syndrome. Prevalence of colobomas is about 2 to 14 per 100,000 births. Microphthalmia, anophthalmia and coloboma (MAC) are structurally related and represent a spectrum of ocular disease that may be present in combination




Diagnostic testing may include a karyotype, choromosomal microarray analysis (CMA) and/or targeted next-generation sequencing (NGS).  The pediatric ophthalmologist encountering these patients should perform a full comprehensive ocular examination, review of systems, obtain a family history and consider examining the parents eyes if available, as colobomas may be unknowingly present in family members. Targeted gene panel testing may be considered. Mutations in the SOX2 gene may account for up to one-fifth of the monogenic causes of MAC. Referral to an eye genetic specialist can assist in ordering the appropriate test and counseling upon return of results.


Patients should receive pre- and post-test genetic counseling.  Selecting genetic testing, interpreting the results and counseling the patients are the responsibility of the physician sending the test. Molecular genetic testing mayidentify the causative genetic defect in up to one-fifth of individuals with an ocular defect in the MAC spectrum. When bilateral anophthalmia or severe microphthalmia is present, a genetic cause is identified in the majority of cases.


Clinical Trial Name: Genetics of Uveal Coloboma Identifier: NCT01778543

Sponsor: National Eye Institute (NEI)

Study Type: Observational



Microphthalmia, Anophthalmia and Coloboma support (MACS):


  • Pediatric ophthalmologists should understand that patients with microphthalmia, anophthalmia or colobomas may have an underlying genetic etiology (even if unilateral)
  • Some genetic conditions associated with colobomas include:
    • CHARGE association
    • Trisomy 13 or 18
    • Cat eye syndrome
    • Jacobsen syndrome
    • Goldenhar syndrome
    • Meckel syndrome
    • Morning glory anomaly
    • Rubinstein-Taybi syndrome
    • Warburg syndrome
    • SOX2-related eye disorders
    • Joubert syndrome
  • When a coloboma is present in a child, consider examining the parents eyes if available.  Colobomas are often autosomal dominant with extremely variable expressivity so parents may unknowingly be affected  
  • Referral to an ophthalmologist with genetic expertise and/or a medical geneticist, often in collaboration with a genetic counselor, is crucial to determine:
    • Accurate diagnosis
    • Surveillance and/or treatment if indicated
    • Family planning
  • Suspect a genetic diagnosis and need guidance? Please submit inquiry to AAPOS Genetics Committee via the AAPOS


Bardakjian T, Weiss A, Schneider A. Microphthalmia/Anophthalmia/Coloboma Spectrum. 2004 Jan 29 [Updated 2015 Jul 9]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.

Nakamura KM, Diehl NN, Mohney BG. Incidence, ocular findings, and systemic associations of ocular coloboma: a population-based study. Arch Ophthalmol. 2011;129(1):69-74.

Skalicky SE, White AJ, Grigg JR, Martin F, Smith J, Jones M, Donaldson C, Smith JE, Flaherty M, Jamieson RV. Microphthalmia, anophthalmia, and coloboma and associated ocular and systemic features: understanding the spectrum. JAMA Ophthalmol. 2013 Dec;131(12):1517-24.