| Topic | Data | Source |
|---|---|---|
| Definition: Microphthalmia | Small eye; axial length/eye volume **<2 SD below age-adjusted mean** | (pqac-00000024, pqac-00000041) |
| Definition: Anophthalmia | **Clinical absence of ocular tissue / no visible globe** | (pqac-00000024, pqac-00000041) |
| Definition: Coloboma | **Missing ocular tissue**; typically inferonasal defects reflect **incomplete optic fissure closure**; may involve iris, ciliary body, retina/choroid/optic nerve and other ocular structures | (pqac-00000024, pqac-00000000) |
| Epidemiology: combined MAC/AMC | **~6–30 per 100,000 live births/children per year** for the MAC spectrum | (pqac-00000038, pqac-00000043) |
| Epidemiology: microphthalmia | **2–17 per 100,000 births** | (pqac-00000040, pqac-00000039) |
| Epidemiology: anophthalmia | **0.6–4.2 per 100,000 births** | (pqac-00000040, pqac-00000039) |
| Epidemiology: coloboma | **2–14 per 100,000 births**; some reviews cite **2–19 per 100,000 live births** | (pqac-00000040, pqac-00000039) |
| Contribution to childhood visual impairment | MAC/AMC account for **~15–20%**, sometimes stated as **up to 20%**, of severe childhood visual impairment/blindness | (pqac-00000040, pqac-00000038, pqac-00000043) |
| Harding et al. 2023 cohort | **50 patients / 44 unrelated families**; phenotype mix: 15 microphthalmia, 2 anophthalmia, 11 coloboma, 22 mixed | (pqac-00000001) |
| Harding et al. 2023: complex ocular features | **22/50 (44%)** had additional ocular features | (pqac-00000001) |
| Harding et al. 2023: systemic involvement | **17/50 (34%)** had systemic manifestations | (pqac-00000001) |
| Harding et al. 2023: developmental delay | Most frequent systemic feature; **8/17 (47%)** of those with systemic involvement had intellectual/developmental delay | (pqac-00000001) |
| Harding et al. 2023: retinal detachment | **7/80 affected eyes (9%)**, all associated with coloboma | (pqac-00000004) |
| Harding et al. 2023: overall molecular diagnostic yield | Testing in **39 families** identified a genetic association in **11/39 (28%)**; paper also reports an overall molecular diagnostic rate of **~33%** in tested cohorts/patients | (pqac-00000001, pqac-00000003, pqac-00000030) |
| Harding et al. 2023: by test modality | Family-level solve rates: **WGS 4/17 (24%)**; **targeted panel 3/18 (17%)**; **aCGH 3/3 (100%)**; **familial variant testing 1/1** | (pqac-00000007, pqac-00000030) |
| Harding et al. 2023: genes solved | Pathogenic variants/CNVs in **SOX2, PAX6, KMT2D, EPHA2, MAB21L2, ALDH1A3, BCOR, FOXE3**, plus large deletions on **chr10, chr11, X** | (pqac-00000030) |
| Recent discovery: MAB21L2 regulatory deletion | **2024**; Ceroni et al.; DOI: https://doi.org/10.1038/s41467-024-53553-2; found an **~113.5 kb homozygous deletion 19.38 kb upstream of MAB21L2**, removing conserved non-coding elements; zebrafish/Xenopus modeling caused **small lens, coloboma, microphthalmia**; supports **non-coding regulatory variants** as MAC causes | (pqac-00000023, pqac-00000036) |
| Recent discovery: FZD5 hypomorphic recessive variant | **2024**; Cortés-González et al.; DOI: https://doi.org/10.1007/s00439-024-02712-y; reported **homozygous FZD5 missense** variant causing **syndromic bilateral ocular coloboma with microcornea**; functional assays showed **hypomorphic/partial loss-of-function** in **WNT signaling**, expanding FZD5 disease mechanisms beyond dominant-negative alleles | (pqac-00000013) |


*Table: This table condenses core disease definitions, epidemiology, major 2023 cohort statistics, and two high-impact 2024 genetic discoveries for microphthalmia with coloboma/MAC. It is useful as a quick reference for clinical, genetic, and knowledge-base curation work.*