Norrie disease

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at January 3, 2017
StartDiseasesNorrie disease

Norrie disease is a rare genetic disorder that occurs in males before or shortly after birth. It often leads to blindness and usually hearing loss, and the symptoms typically worsen over time. Norrie disease is also known as Anderson-Warburg syndrome, Episkopi blindness, and fetal iritis syndrome.

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Definition & Facts

Norrie disease is caused by a mutation in the NDP gene, a gene that occurs on the X chromosome. The disease only affects males and typically leads to blindness at birth or shortly after. It is a very rare condition, and specialists are unsure of how many people have been affected. No one racial or ethnic group has a higher rate of occurrence. The disease was first discovered in the 1960s by a Danish ophthalmologist.

The primary characteristic of Norrie disease is retinal degeneration, which usually begins before birth and leads to blindness. The retina is a layer of nerve cells at the back of the eye that is responsible for converting light into nerve signals. Normally, retinas should be connected to a layer of supporting tissue, but the retinas in individuals with Norrie disease separate from the tissue. This causes a mass of partially-formed retinal cells to develop behind the pupils.

Symptoms & Complaints

People with Norrie disease experience a number of eye and vision problems. They often have leukocoria, or pupils that appear white. The lenses of the eyes may also appear cloudy at birth or become cloudy over time. Some individuals experience phthisis bulbi or the shrinking of the eyeballs.

Cataracts frequently occur as a result of Norrie disease, and sometimes they completely cover the lenses of the eyes. Other common symptoms include dilated pupils and an increase in pressure in the eyes.

Norrie disease also usually causes hearing loss that worsens over time. This occurs because of an abnormality in the cochlea, which is located in the inner ear. Hearing loss usually starts in early childhood and becomes severe in adulthood. However, the severity of hearing loss varies between individuals. Between 30 and 50 percent of people with Norrie disease have cognitive delays and do not reach normal developmental milestones, even milestones that are unrelated to vision or hearing.

Causes

Norrie disease is caused by an X-linked recessive trait, which is an abnormal or mutated gene on the X chromosome. NDP is the specific gene responsible for Norrie disease. It tells the body's cells to create the norrin protein. It likely aids in the development of blood vessels that carry blood to the retina. When the retina doesn't receive enough blood flow, it doesn't develop properly and can separate from the connecting tissue.

Because females have two X chromosomes, one of their X chromosomes will be "normal" even if the other X chromosome has the mutated NDP gene. Therefore, females are very rarely affected by the disease. They can, however, be genetic carriers of the disease and pass it on to male children. In a few rare situations, females have had some minor symptoms, but the disease primarily affects males. Males only have one X chromosome, so if the mutated NDP gene is present on the X chromosome, they will have the disease. 

Diagnosis & Tests

As with most genetic conditions, doctors consider the patient's family history to determine whether a patient has Norrie disease. There are many diseases that lead to vision loss, but if an infant with vision loss comes from a family where the mutated gene is present, Norrie disease is likely the cause. Doctors can also diagnose the disease by observing the eye. If they notice a grayish-yellow mass of cells behind the pupil, it may indicate that the patient has Norrie disease.

Over time, doctors can also observe a patient as the condition progresses. If doctors notice many of the common symptoms of Norrie disease developing over a period of weeks or months, they can make a diagnosis.

To confirm the condition, patients can have a genetic test at a testing lab. Specialists can use a few tests to determine whether the NDP gene is mutated. Sequence analysis is a genetic test that can successfully identify the disease in about 85 percent of males who are affected. A deletion/duplication analysis test can confirm the presence of the disease in the other 15 percent of affected males.

Treatment & Therapy

While there is no cure for Norrie disease, people with the condition can undergo treatment to manage their symptoms. Many patients with the disease work with a team of specialists to create an individualized treatment plan. For infants or children, pediatricians often work with ophthalmologists who specialize in eye abnormalities and audiologists who specialize in hearing loss.

If cataracts are a serious problem for a person with Norrie disease, surgery could be an option to remove the cloudy lens. Surgery is also sometimes an option for re-attaching retinas that have detached.

When hearing loss becomes an issue, patients can benefit from using hearing aids. If hearing loss becomes very severe, individuals can restore some of their hearing ability with a cochlear implant, a device placed in the inner ear that helps the cochlea send sound signals to the brain.

Early diagnosis and intervention is essential for managing symptoms. When young children with the disease receive therapy, personalized education, or medical and social services, it can help them function better during adulthood. Learning to manage vision and hearing loss from a young age helps as the symptoms progressively worsen.

Prevention & Prophylaxis

Norrie disease, like most genetic disorders, cannot be prevented. If a male child inherits the mutated NDP gene, he will develop the disease. However, early diagnosis and treatment may prevent some symptoms from worsening and can help the patient learn to manage some symptoms from a young age.

Parents who both have a history of Norrie disease in their families or who believe they may be carriers can visit a genetic counselor to understand their chances of passing the gene on.