Syndromic microphthalmia-anophthalmia-coloboma

Syndromic microphthalmia-anophthalmia-coloboma (MAC) refers to a group of rare developmental eye disorders in which abnormally small eyes (microphthalmia), absent eyes (anophthalmia), or gaps in ocular structures (coloboma) occur alongside additional systemic abnormalities affecting other organ systems. Unlike isolated MAC, the syndromic forms are characterized by the presence of extra-ocular features, which may include intellectual disability, craniofacial anomalies, cardiac defects, skeletal malformations, brain abnormalities, renal anomalies, and genital malformations, depending on the specific underlying genetic cause. The eye findings result from disrupted development during early embryogenesis, when the optic vesicle and optic fissure fail to form or close properly. The severity of visual impairment ranges from mild visual reduction in cases of small colobomas to complete blindness in bilateral anophthalmia. Numerous genetic causes have been identified for syndromic MAC, including mutations in genes such as SOX2, OTX2, PAX6, FOXE3, BMP4, GDF6, STRA6, ALDH1A3, RAX, VSX2, and others. The inheritance pattern varies depending on the specific syndrome and causative gene, encompassing autosomal dominant, autosomal recessive, and X-linked patterns. Chromosomal abnormalities and copy number variants can also be responsible. Genetic testing, including chromosomal microarray and gene panel or exome sequencing, is recommended for diagnosis and genetic counseling. There is currently no cure for syndromic MAC. Management is multidisciplinary and supportive, involving ophthalmologists, geneticists, and specialists relevant to the associated systemic features. Ocular management may include conformers or prosthetic eyes to promote orbital growth in anophthalmia or severe microphthalmia, surgical correction of coloboma-related complications such as retinal detachment, and low-vision rehabilitation. Associated anomalies such as cardiac defects or renal malformations require appropriate specialist care. Early intervention programs and developmental support are important for children with associated intellectual disability.

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