anophthalmia/microphthalmia-esophageal atresia syndrome

Anophthalmia or microphthalmia-esophageal atresia syndrome is a very rare multisystem condition that primarily affects eye formation and the upper digestive tract. It is caused by changes in the SOX2 gene, which provides instructions for a transcription factor critical for early embryonic development of the eyes, brain and foregut. Most individuals present in the newborn period with absent or very small eyes and difficulty swallowing due to esophageal atresia, often accompanied by a tracheoesophageal fistula. Both males and females can be affected, and symptoms usually become apparent at or shortly after birth. Fewer than one in a million people are thought to have this syndrome worldwide.

The clinical picture spans several organ systems. Ocular findings are the most striking. Many infants are born with complete absence of one or both eyes, while others have very small eyes. Optic nerve aplasia is consistently reported, and some children develop additional eye findings such as cataracts, corneal opacity or coloboma. Because vision is often severely limited, early referral to low-vision services is important. The gastrointestinal hallmark is esophageal atresia, sometimes connected to the airway by a tracheoesophageal fistula, leading to feeding difficulties, choking and early need for surgical repair. Hearing is also affected; bilateral sensorineural hearing impairment is common and may require hearing aids or cochlear implantation. From a cognitive and developmental standpoint, all reported children have global developmental delay, and many are shorter than expected for age. Less frequent features include microcornea or sclerocornea. Not all individuals experience every feature, and severity varies considerably, even among people with the same genetic change.

The syndrome results from pathogenic variants in the SOX2 gene located on chromosome 3q. The SOX2 protein is a transcription factor that helps guide early formation of the eyes, brain and foregut, so disrupted function can lead to the combination of eye malformations and esophageal anomalies seen in this condition. The disorder follows an autosomal dominant inheritance pattern, meaning a single altered copy of SOX2 can cause disease. An affected individual has a 50 percent chance of passing the variant to each child, regardless of the child’s sex. However, the way the condition appears can differ widely from one person to the next, a phenomenon known as variable expressivity. Genetic counseling is recommended for families to discuss testing of at-risk relatives and reproductive options.

Currently, management focuses on supportive care and symptom management tailored to each person’s needs. Surgical repair of the esophageal atresia and any tracheoesophageal fistula is usually performed in early infancy to establish safe feeding. Ocular prostheses, low-vision training and, when possible, surgical intervention for cataracts or coloboma can enhance visual function and cosmetic outcome. Hearing aids or cochlear implants address sensorineural hearing loss, and early speech and language therapy supports communication. Because global developmental delay is universal, ongoing physical, occupational and special-education services are foundational. Long-term care is best coordinated by a multidisciplinary team that may include pediatric surgeons, ophthalmologists, otolaryngologists, developmental pediatricians and genetic counselors. Regular surveillance for growth, nutritional status, and emerging neurological or endocrine issues helps detect complications early, allowing timely intervention. Families should work closely with their healthcare team to review available therapies and monitoring plans as new information becomes available.

Outcomes depend on the severity of eye malformations, success of early esophageal surgery, associated health issues and access to specialized care. Many children achieve good nutritional status after surgical repair and make developmental progress with intensive therapies, although significant visual impairment and cognitive challenges often persist. Severity and symptoms vary widely between individuals, so long-term milestones cannot be predicted for any one child. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and genetic counselors who can provide up-to-date guidance and support.