The majority of patients with microphthalmos and colobomas have genetic disorders. This is a survey of non-inherited, sporadic microphthalmos. Such cases may occur in the Goldenhar, CHARGE and VATER associations; it may also be due to teratological agents, for instance maternal ingestion of drugs, maternal infection, fever or irradiation. In these cases it is possible that neural crest cell development is abnormal. Some drugs, for instance retinoic acid are regulators of Hox genes which control an ordered sequence of differentiation; coloboma or microphthalmos may appear if deregulation occurs.

Large choristomas of the anterior segment of the eye may be associated with microphthalmos or anophthalmos. Encephaloceles or orbital tumours may deform the growing eye and are another cause of non-inherited microphthalmos.