Chapter 16 - Developmental eye disorders

Abstract

Microphthalmia, anophthalmia, and ocular coloboma, collectively considered together under the acronym MAC, represent a vast clinical spectrum that is a common cause of childhood visual impairment. MAC conditions carry a profound lifelong impact for both child and family, with significant social, emotional, and health implications including elevated early mortality rates in syndromic cases. Most MAC cases are sporadic; around two-thirds are syndromic with up to one-third displaying craniofacial anomalies. Inheritance can be autosomal or X-linked, and in both cases, it can be either dominant or recessive. The occurrence of de novo mutations, mosaicism and incomplete penetrance makes clinical prediction of inheritance patterns challenging. This group of conditions is highly genetically heterogenous with over 90 disease-causing genes already identified. Genomic testing of MAC patients using high-throughput sequencing is increasingly successful in identifying the underlying cause. Given that de novo mutations are common in apparently sporadic cases (i.e. the majority of individuals with MAC), testing of parent-offspring trios is the most effective strategy in this group of patients.