OMIM ID:
Coloboma, Isolated
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Colobomas of the uveal tract are often found in association with other ocular anomalies including those with systemic disease. They are usually located in the inferonasal quadrant as a result of defective closure of the embryonic fissure in the optic cup. Most involve the nearly complete iris and resemble a keyhole but they may also be partial resulting in an oval pupil. They are sometimes unilateral in which case the involved iris may be more heavily pigmented than the contralateral one. They may involve only the iris (simple coloboma) but often are more extensive with involvement of the ciliary body, retina, lens, choroid, and even the optic nerve. They are frequently associated with microphthalmia (or microphthalmia with cyst [5.6%]) and microcornea (79%).
Systemic Features
None by definition.
Genetics
Inheritance
Isolated colobomas are clinically and genetically heterogeneous resulting from mutations in SHH (7q36.3), PAX6 (11p13), and ABCB6 (2q35) among others. Large pedigrees with typical autosomal dominant transmission patterns have been reported.
Homozygous mutations in SALL2 (14q11.1-q12.1) have also been reported in patients with isolated colobomas. Studies of sall2-deficient mice show defects in closure of the anterior optic fissure while posterior closure proceeds normally.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission