SOX2 Anophthalmia Syndrome - An Overview

What Is SOX2 Anophthalmia Syndrome?

SOX2 anophthalmia syndrome is an uncommon genetic disease with a unique set of characteristics. It is characterized by abnormal development of one or both eyes and abnormalities in other body parts, including the brain and other organs. SOX2 anophthalmia syndrome is believed to impact approximately one in 250,000 individuals, with an estimated 10 to 15 per cent of those diagnosed with anophthalmia in both eyes having this specific syndrome. SOX2 anophthalmia syndrome is also known as AEG syndrome, SOX2-related eye disorders, anophthalmia-esophageal-genital syndrome, and syndromic microphthalmia. The issues with abnormal eye formation can result in vision loss.

In most cases, this syndrome will affect both eyes, with more severe abnormalities in one eye than the other. Other body parts can also be affected by this syndrome. With brain abnormalities, the affected individual may experience seizures, developmental delays in motor and cognitive skills, and delayed growth when compared to normal children. Some individuals may be born with an abnormal connection between the food pipe and the windpipe; this may lead to blockage in the esophagus, known as esophageal atresia. Other abnormalities include genital abnormalities, which are predominantly seen in males. Male genital abnormalities include an unusually small penis and undescended testes.

What Is the Cause of SOX2 Anophthalmia Syndrome?

SOX2 anophthalmia syndrome is a genetic disorder that is caused by variations in the SOX2 (sex-determining region Y-box 2) gene. This gene is present on chromosome 3q26.3-q27. This gene plays a crucial role in providing instructions for producing a protein that is involved in the development of many different tissues, including the eyes, brain, and other organs, during the early development of the fetus.

The SOX2 protein encodes a transcription factor of other genes, mainly those significant for typical eye development. Any variations occurring in the SOX2 gene prevent the normal production and function of SOX2 protein. The abnormalities and lack of production of SOX2 protein throw into confusion in the gene activity involved in the development of the eyes, brain, and other important body parts. Abnormal development of the SOX2 gene causes the clinical manifestation of SOX2 anophthalmia syndrome.

Sox2 anophthalmia syndrome is a disorder with autosomal dominant inheritance, meaning a copy of a mutated gene from any of the parents is the only responsible factor for the disease. An individual whose parent has the mutated gene has a 50 per cent chance of getting this disease. Most individuals with Sox2 anophthalmia will be the first in their family history to have the SOX2 mutation, with no history of SOX2 anophthalmia syndrome in their family. In rare cases, this condition may have been inherited from an unaffected father or mother with gene variations only in their sperm or egg cells.

What Are the Signs and Symptoms of SOX2 Anophthalmia Syndrome?

The signs and symptoms of SOX2 anophthalmia syndrome may vary widely among affected individuals; some of the common signs and symptoms include:

• Anophthalmia or Microphthalmia: The main characteristic feature of SOX2 anophthalmia syndrome is the absence of one or both eyes (anophthalmia) or severely underdeveloped eyes (microphthalmia). This is a developmental anomaly resulting from abnormalities in early fetal development.

• Abnormalities in the Eyes: Individuals with SOX2 anophthalmia syndrome may also have other abnormalities in the eyes in addition to anophthalmia or microphthalmia, which may include cataracts, retinal dysplasia (abnormal development of the retina), and coloboma (a gap or notch in the structures of the eyes).

• Seizures - Due to abnormalities in the brain during development, individuals with SOX2 anophthalmia syndrome may develop seizures, which are an intermittent abnormality of the central nervous system occurring because of sudden, abnormal, disorderly discharge of cerebral neurons. It may appear as a combination of loss of consciousness, sensation disturbance, bodily function loss, or uncontrollable involuntary movements. When there is a severe, repeated seizure, it is referred to as epilepsy.

• Developmental Delays - Infants with this condition will delay achieving motor skills such as walking, speech, and other cognitive skills, such as learning, social, and emotional skills.

• Esophageal Atresia - This is a developmental defect causing complete blockage of the esophagus, resulting in frothy white bubbles in the baby's mouth and coughing or choking when feeding.

• Cryptorchidism - The testis will be present in the inguinal canal. This causes the absence of one or both testes from the scrotum, leading to failure of testis formation.

• Micropenis - The penis will be abnormally smaller than usual. In general, the normal penis will be approximately 30 mm, whereas micropenis will be less than 20 to 25 mm.

How Is SOX2 Anophthalmia Syndrome Diagnosed?

As SOX2 anophthalmia syndrome is a very rare entity, the diagnosis of this condition is a challenging task for healthcare professionals. An investigation including a multidisciplinary team of ophthalmologists, neurologists, geneticists, and other specialists is necessary for an accurate diagnosis and effective treatment.

• Physical Examination: A thorough physical examination, consisting of eye examination and neurodevelopmental features, is required to identify this condition's characteristic signs.

• Eye Checkup: A complete eye checkup is necessary to diagnose ocular anomalies, such as anophthalmia, microphthalmia, and other abnormalities involving the eyes.

• Imaging Techniques: Imaging studies, including magnetic resonance imaging (MRI) of the brain, are essential to assess for any abnormalities in the brain and guide accurate treatment.

• Genetic Testing: Molecular genetic testing helps identify any changes associated with the SAS gene.

What Is the Treatment for SOX2 Anophthalmia Syndrome?

There is a permanent cure for SOX2 anophthalmia syndrome. The main aim of the treatment is to address the presenting illness of the individual and manage their overall health.

• Eye Prosthetics and Surgical Treatment: A customized eye prosthesis will help improve cosmesis in individuals with anophthalmia or severe microphthalmia. Surgery for correcting eye abnormalities, such as orbital reconstruction, will help improve the aesthetics.

• Developmental Support: A multidisciplinary team will provide speech therapy, occupational therapy, and behavioral interventions to address developmental delays.

• Genetic Counseling: Genetic counseling will be offered to individuals affected by SOX2 anophthalmia syndrome and their families.

Conclusion:

SOX2 anophthalmia syndrome is a very rare genetic disorder that occurs due to a mutation in the SOX2 gene. The main characteristic feature of this syndrome is the abnormal development of one or both eyes and other body parts, including the brain. The affected individuals will suffer from vision loss, development delays, and other neurological conditions. Treatment involves a multidisciplinary team of doctors, such as eye specialists, speech therapists, and neurologists. Advancements in genetic technologies will help develop new treatment approaches in the future.