Anophthalmia/microphthalmia-esophageal atresia syndrome

Description

Anophthalmia/microphthalmia-esophageal atresia (AEG) syndrome is a rare disorder that is characterized by the abnormal development of the eyes and other parts of the body, including the tube that carries food from the mouth to the stomach (esophagus).

People who have AEG syndrome are usually born without one or both eyes (anophthalmia), although some individuals have underdeveloped and abnormally small eyes (microphthalmia). People who have anophthalmia have no vision in the affected eye, but people who have microphthalmia may or may not have significant vision loss.

Affected individuals who have some remaining eye tissue can have additional eye abnormalities. Some people may be missing pieces of tissue in the structures that form the eye (coloboma), or the nerves that carry signals between the eyes and the brain may be underdeveloped (optic nerve hypoplasia). The presence of other eye problems can worsen an affected person's vision.

Some people with AEG syndrome are born with a blocked esophagus (esophageal atresia), which is often accompanied by an abnormal connection between the windpipe (trachea) and the esophagus (tracheoesophageal fistula). Additional features of AEG syndrome can include brain abnormalities, slow growth, delayed development of motor skills (such as walking), and intellectual disabilities. Affected individuals may also have genital abnormalities, which can include undescended testes (cryptorchidism) and an unusually small penis.

Frequency

AEG syndrome is estimated to affect 1 in 250,000 individuals.

Causes

Variants (also called mutations) in the SOX2 gene cause AEG syndrome. This gene provides instructions for making a protein that regulates the activity of other genes, including those that are important for the normal development of the eyes.

The SOX2 protein plays a critical role in the formation of many different tissues and organs during embryonic development. Variants in the SOX2 gene can cause cells to produce a version of the SOX2 protein that does not function properly. As a result, the protein cannot regulate the activity of genes that are essential for the development of the eyes and other parts of the body. Abnormal development of these structures causes the signs and symptoms of AEG syndrome.

Inheritance

AEG syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases of this condition result from new (de novo) variants in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

Autosomal dominant inheritance with a new (de novo) mutation. Credit: U.S. National Library of Medicine.

In a small number of cases, people with AEG syndrome have inherited the altered gene from an unaffected parent who has a SOX2 variant only in their sperm or egg cells. This phenomenon is called germline mosaicism.

Other Names for This Condition

• AEG syndrome
• Anophthalmia-esophageal-genital syndrome
• MCOPS3
• SOX2 anophthalmia syndrome
• SOX2 disorder
• SOX2 syndrome
• SOX2-related eye disorders
• Syndromic microphthalmia type 3

Where this page came from

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