Goyal S, Tibrewal S, Ratna R, Vanita V. Genetic and environmental factors contributing to anophthalmia and microphthalmia: Current understanding and future directions. World J Clin Pediatr 2025; 14(2): 101982 [DOI: 10.5409/wjcp.v14.i2.101982]
Corresponding Author of This Article
Vanita Vanita, PhD, Professor, Department of Human Genetics, Guru Nanak Dev University, Grand Trunk Road, Off NH 1, Amritsar 143005, Punjab, India. vanita_kumar@yahoo.com
Research Domain of This Article
Genetics & Heredity
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Shiwali Goyal, Department of Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Rockville, MD 20852, United States
Shailja Tibrewal, Department of Pediatric Ophthalmology, Dr. Shroff’s Charity Eye Hospital, New Delhi 110002, Delhi, India
Shailja Tibrewal, Ria Ratna, Department of Ocular Genetics (Center for Unknown and Rare Eye Diseases), Dr. Shroff’s Charity Eye Hospital, New Delhi 110002, Delhi, India
Vanita Vanita, Department of Human Genetics, Guru Nanak Dev University, Amritsar 143005, Punjab, India
Author contributions: Goyal S was responsible for data collection and manuscript writing; Goyal S, Tibrewal S, and Ratna R were responsible for editing of the manuscript; Vanita V was responsible for study design; all the authors have read and approved the final version of this manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Vanita Vanita, PhD, Professor, Department of Human Genetics, Guru Nanak Dev University, Grand Trunk Road, Off NH 1, Amritsar 143005, Punjab, India. vanita_kumar@yahoo.com
Received: October 3, 2024 Revised: February 19, 2025 Accepted: February 25, 2025 Published online: June 9, 2025 Processing time: 165 Days and 16.1 Hours
Abstract
Anophthalmia is defined as a complete absence of one eye or both the eyes, while microphthalmia represents the presence of a small eye within the orbit. The estimated birth prevalence for anophthalmia is approximately 3 per 100000 live births, and for microphthalmia, it is around 14 per 100000 live births. However, combined evidence suggests that the prevalence of these malformations could be as high as 30 per 100000 individuals. Microphthalmia is reported to occur in 3.2% to 11.2% of blind children. Anophthalmia and microphthalmia (A/M) are part of a phenotypic spectrum alongside ocular coloboma, hypothesized to share a common genetic basis. Both A/M can occur in isolation or as part of a syndrome. Their complex etiology involves chromosomal aberrations, monogenic inheritance pattern, and the contribution of environmental factors such as gestational-acquired infections, maternal vitamin A deficiency (VAD), exposure to X-rays, solvent misuse, and thalidomide exposure. A/M exhibit significant clinical and genetic heterogeneity with over 90 genes identified so far. Familial cases of A/M have a complex genetic basis, including all Mendelian modes of inheritance, i.e., autosomal dominant, recessive, and X-linked. Most cases arise sporadically due to de novo mutations. Examining gene expression during eye development and the effects of various environmental variables will help us better understand the phenotypic heterogeneity found in A/M, leading to more effective diagnosis and management strategies. The present review focuses on key genetic factors, developmental abnormalities, and environmental modifiers linked with A/M. It also emphasizes at potential research areas including multiomic methods and disease modeling with induced pluripotent stem cell technologies, which aim to create innovative treatment options.
Core Tip: Anophthalmia (absence of one or both eyes) and microphthalmia (small eye within the orbit) are rare congenital conditions, affecting up to 30 per 100000 individuals. These malformations can occur independently or as a part of a syndrome, with complex genetic basis involving over 90 genes. Environmental factors like maternal infections, vitamin A deficiency, and toxin exposure also contribute to their development. Both conditions exhibit significant variability, making diagnosis and management challenging. This review discusses genetic and environmental influences on anophthalmia and microphthalmia, highlighting promising research areas such as multiomic approaches and stem-cell based models for potential therapeutic advancements.
