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Key Points

  • Microphthalmia, anophthalmia, and coloboma represent a spectrum of developmental anomalies of the eye known as MAC.

  • Prevalence is 1 in 10,000 births. Approximately 10% of affected children have a chromosome abnormality. There may be an increased incidence of MAC in mothers older than age 40 and in multiple gestation.

  • Nomograms exist for normal fetal eye measurements at 12 to 37 weeks’ gestation. Refer for targeted fetal anatomical evaluation because of high likelihood of associated anomalies.

  • Strongly associated with chromosome abnormalities and single-gene disorders.

  • Karyotype is indicated. If bilateral anophthalmia is present, consider DNA testing for SOX2 mutations.

  • Refer for consultation with medical geneticist and pediatric ophthalmologist.

  • Progress depends on severity of eye defects and presence of associated anomalies. Recurrence risk depends on syndromic diagnosis.

  • Many developmental gene mutations are being identified as underlying basis of MAC.


Microphthalmia is one stage in a spectrum of developmental abnormalities that affect the eye, with coloboma at the milder end and anophthalmia at the severe end. Collectively the eye defect is known as MAC (microphthalmia, anophthalmia, coloboma). Although microphthalmia and anophthalmia can present as isolated findings, they are more commonly appreciated as part of syndromes involving multiple malformations (Bronshtein et al., 1991). Both are associated with abnormalities of the central nervous system.

Warburg (1993) proposed a phenotypic classification of microphthalmia that consists of three groups: genetic (monogenic and chromosomal), prenatally acquired (teratologic agents and intrauterine deformations), and associations. Genetic disorders commonly result in malformations of the eye, whereas prenatally acquired insults result in disruption or deformation of an initially normal eye.

The eye derives from three embryologic germ layers. Neuroectoderm gives rise to the optic vesicle; neural crest cells are responsible for migration to the anterior chamber of the developing eye. Ectoderm is responsible for the formation of the lens placode. Neuroectodermal and mesodermal cells participate in the closure of the optic fissure. The variety of cells and tissue types involved explains variability of phenotypic abnormalities of the eye (see Table 29-1) (Warburg, 1993). The embryonic optic fissure is formed from invagination along the inferior aspect of the optic cup and optic stalk at the 5-to-8-mm stage of gestation. This fissure allows the ingress of the hyaloid artery and egress of retinal axons through the optic nerve. In the normal eye, the embryonic optic fissure closes at 33 to 44 days after conception. If the fissure fails to fuse, a defect in the neuroectodermal and uveal tissues will be produced, forming a coloboma. The coloboma is a layer of sclera lined by maldeveloped neuroectoderm (Leatherbarrow et al., 1990). Colobomas of the uvea are frequently associated with microphthalmia and microcornea. Congenital cystic eye is a malformation that results from failure of invagination of the optic vesicle. Cysts frequently develop from proliferation of neuroectodermal tissue at the edge of the persistently open ...

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