Early-onset glaucoma

Glaucoma is a group of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. This damage can lead to reduction in peripheral vision and eventual blindness. Other signs and symptoms may include bulging eyes, tearing, and abnormal sensitivity to light (photophobia).

In most people with glaucoma, the damage to the optic nerves is caused by increased pressure within the eyes (intraocular pressure). Intraocular pressure depends on a balance between fluid entering and leaving the eyes, coupled with adequate flow through the veins draining the area.

Usually glaucoma develops in older adults, in whom the risk of developing the disorder may be affected by a variety of medical conditions including high blood pressure (hypertension) and diabetes mellitus, as well as family history. The term "early-onset glaucoma" may be used when the disorder appears before the age of 40. The risk of early-onset glaucoma depends mainly on heredity.

Structural abnormalities that impede fluid drainage in the eye may be present at birth, resulting in symptoms by about 5 years of age. Such abnormalities may be part of a genetic disorder that affects many body systems, called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma.

Other individuals experience early onset of the most common adult form of glaucoma, called primary open-angle glaucoma. If this disorder develops during childhood or early adulthood, it is called juvenile open-angle glaucoma.

Primary congenital glaucoma affects approximately 1 in 10,000 people. Its frequency is higher in the Middle East. Juvenile open-angle glaucoma affects about 1 in 50,000 people. Open-angle glaucoma is much more common after the age of 40, affecting about 1 percent of the population worldwide.

Mutations in the CYP1B1 and MYOC genes cause early-onset glaucoma.

Approximately 10 percent to 33 percent of people with juvenile open-angle glaucoma have mutations in the MYOC gene. MYOC mutations have also been detected in some people with primary congenital glaucoma. The MYOC gene provides instructions for producing a protein called myocilin. Myocilin is found in certain structures of the eye, called the trabecular meshwork and the ciliary body, that regulate the intraocular pressure.

Researchers believe that myocilin functions as part of a protein complex. Mutations may alter the protein in such a way that the complex cannot be formed. Defective myocilin that is not incorporated into functional complexes may accumulate in the trabecular meshwork and ciliary body. The excess protein may prevent sufficient flow of fluid from the eye, resulting in increased intraocular pressure and causing the signs and symptoms of early-onset glaucoma.

Between 20 percent and 40 percent of people with primary congenital glaucoma have mutations in the CYP1B1 gene. CYP1B1 mutations have also been detected in some people with juvenile early-onset glaucoma. The CYP1B1 gene provides instructions for producing a form of the cytochrome P450 protein. Like myocilin, this protein is found in the trabecular meshwork, ciliary body, and other structures of the eye.

The role of the CYP1B1 protein in the development or function of the eye is not well understood. Researchers have suggested that the protein may be involved in a process in the cornea that regulates the secretion of fluid inside the eye. If this fluid is produced in excess, the high intraocular pressure characteristic of glaucoma may develop.

Some researchers have proposed that the CYP1B1 protein may interact with myocilin. Individuals with mutations in both the MYOC and CYP1B1 genes may develop glaucoma at an earlier age than do those with mutations in only one of the genes. Mutations in other genes, some of which have not been identified, may also be involved in early-onset glaucoma.

Read more about the CYP1B1 and MYOC genes.

Early-onset glaucoma can have different inheritance patterns. Primary congenital glaucoma is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Juvenile open-angle glaucoma is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some families, primary congenital glaucoma may also be inherited in an autosomal dominant pattern.