From the Guidelines
Coloboma is primarily caused by incomplete closure of the optic fissure during embryonic eye development, typically occurring between the 5th and 7th weeks of gestation, and can be associated with genetic syndromes such as CHARGE syndrome, as noted in the european society for immunodeficiencies guidelines for the management of patients with congenital athymia 1.
Causes of Coloboma
The causes of coloboma can be genetic, with mutations in genes like PAX6, CHD7, and CHARGE syndrome-associated genes being common culprits, as well as environmental factors during pregnancy, including maternal exposure to alcohol, certain medications, infections, and nutritional deficiencies 1.
- Genetic factors: mutations in genes like PAX6, CHD7, and CHARGE syndrome-associated genes
- Environmental factors: maternal exposure to alcohol, certain medications, infections, and nutritional deficiencies
- Associated syndromes: CHARGE syndrome, cat-eye syndrome, or Patau syndrome (trisomy 13)
Clinical Features
Coloboma can occur sporadically without any identifiable cause or as part of various genetic syndromes, and the condition affects different parts of the eye depending on which portion of the optic fissure fails to close properly, potentially involving the iris, retina, choroid, or optic nerve, as discussed in the vision rehabilitation preferred practice pattern 1 and the acr appropriateness criteria for orbital imaging and vision loss-child 1.
- Iris notches with minimal visual impact
- Extensive defects causing significant vision impairment
- Associated systemic conditions, such as heart defects, atresia of nasal choanae, retardation of growth and development, genitourinary anomalies, and ear anomalies in CHARGE syndrome 1
From the Research
Causes of Coloboma
The causes of coloboma can be attributed to various factors, including:
- Incomplete closure of the embryonic fissure, which begins around the fifth week of gestation 2
- External factors affecting the fetus during pregnancy 2
- Genetic mutations, such as an autosomal dominant mutation in the Pax gene, which is linked to bilateral colobomas 2
- Defective closure of the fetal fissure, which can affect any part of the globe traversed by the fissure from the iris to the optic nerve 3
- Maldevelopment of optic fissure closure during early eye morphogenesis, which can be caused by both inherited and environmental influences 4
Genetic Factors
Genetic factors play a significant role in the development of coloboma, with several genes identified as being associated with the condition, including:
- The Pax gene, which is linked to bilateral colobomas 2
- Other genes that influence optic fissure closure, which have been identified through research on the genetic causes of coloboma 4
Environmental Factors
Environmental factors, such as those affecting the fetus during pregnancy, can also contribute to the development of coloboma 2
Mechanism of Coloboma Formation
The formation of a coloboma can occur due to the distinct nature of the closure of the embryonic fissure, which starts centrally within the eye and progresses both anteriorly and posteriorly 2 This closure process can result in an optic nerve coloboma without an associated iris coloboma 2