Norrie Disease

What is Norrie Disease?

Norrie disease is a genetic eye disease that typically causes complete blindness at birth or within the first few months of life. Norrie disease affects the development of your baby’s retina and its blood vessels. The retina is a lining of cells at the back of each eye that detects light and color. A healthy retina is essential for vision.

In Norrie disease, a genetic mutation (change) prevents the retinas in your baby’s eyes and the retinal blood vessels from developing normally. When this happens, the retina can detach and hemorrhages can build underneath it, causing it to become fibrotic and move up to right behind the lens of your baby’s eyes. This prevents your baby’s eyes from working as they should. While a small percentage of babies can perceive some light at birth, most are born with complete blindness in one or both eyes.

The genetic mutation that affects your baby’s vision can also affect other aspects of their development. Therefore, Norrie disease has many features that extend beyond vision loss.

What are the features of Norrie disease?

Vision loss (at birth or soon after) is the primary feature of Norrie disease. But babies born with Norrie disease may also have:

• Hearing loss. Norrie disease may also affect the development of the inner ear. Therefore, mild hearing loss may start in early childhood and gradually get worse. As the hearing loss progresses, your child may experience symptoms like tinnitus. Some people with Norrie disease have significant hearing loss by age 35.
• Behavioral changes. Norrie disease may impact your child’s behavior. A common example of a behavioral change is pseudobulbar affect, which affects about 1 in 4 people with Norrie disease.
• Developmental delays. Some babies and children need more time to reach developmental milestones like sitting up or walking.
• Autism spectrum disorder. About 1 in 4 people with Norrie disease may also have autism or autism-like signs.
• Seizure disorders. Though less common than other features, seizures may affect about 1 in 10 people with Norrie disease.
• Peripheral vascular disease. Some people with Norrie disease develop venous ulcers or other problems related to blood circulation.

There’s no set pattern for which features a baby may have. Even babies within the same family may experience different features. That’s why every baby with Norrie disease needs individualized care.

How common is Norrie disease?

Norrie disease is rare. It was first described in 1927 by Danish ophthalmologist Gordon Norrie. No statistics are available for its frequency in the general population, but it’s likely to occur in 1 out of several hundred thousand people.

Who does it affect?

Norrie disease mostly affects male babies. It rarely affects female babies, and when it does, the manifestations and symptoms are mild. There are no associations with race or ethnicity.

What are the signs of Norrie disease?

There are many signs of Norrie disease that an ophthalmologist can see through an eye exam. These include:

• A grayish-yellow mass near the back of the eye (pseudoglioma). This mass is made of under- or abnormally-developed retina.
• Retinas that pull away from their supporting tissue (retinal detachment).
• Pupils that look white (leukocoria).
• Widened (dilated) pupils.
• Underdeveloped irises (iris hypoplasia).
• Irises that adhere to the lens (posterior synechiae) or cornea (anterior synechiae).
• Eyes that are smaller than usual (microphthalmia).
• Raised pressure in the eye (intraocular pressure). This can cause pain as a primary symptom.
• Bleeding in the center of the eye (vitreous hemorrhage).
• Clouding of the eye’s lens (cataract).
• Shrinking of the non-seeing eyeball (phthisis bulbi).

Not all of these signs show up right away. Some may be visible at birth, while others develop months or years later.

Signs are things that healthcare providers can see through an exam. Some signs may also be visible to you or others. Symptoms, on the other hand, are what your child feels.

What are the symptoms of Norrie disease?

The symptoms of Norrie disease can vary widely depending on the features of the disease. Eye pain is one symptom all babies with Norrie disease may feel due to increased pressure in their eyes, but this is quite uncommon. If the cornea develops calcium deposits in it (band keratopathy), this may be a source of irritation and pain. Your child’s ophthalmologist will check their eye pressure regularly.

Other symptoms may relate to hearing loss and other associated disorders. Talk to your child’s care team to learn what symptoms you should be aware of.

What causes Norrie disease?

A genetic mutation causes Norrie disease. The specific gene affected is the NDP gene. The NDP gene tells your body how to create a protein called norrin, which plays an important role in cell signaling and specialization. Specifically, norrin helps your retina develop properly. It also supports the creation (angiogenesis) of blood vessels that supply blood to your retina and inner ear.

Mutations to the NDP gene cause norrin to work incorrectly. Such mutations can lead to several different genetic eye disorders, known as NDP-related retinopathies. Norrie disease is the most severe form.

How is Norrie disease inherited?

The mutated NDP gene is located on the X chromosome. This is one of two sex chromosomes (X and Y) that carry mutations you can inherit. There are different patterns of inheritance, or paths for a mutation to follow. People inherit Norrie disease in an X-linked recessive pattern.

Conditions inherited in an X-linked recessive pattern usually affect male babies and are rare among female babies. This is because male babies only have one X chromosome and therefore only need to inherit one copy of a mutated gene to develop the condition.

A male baby has a 50% chance of inheriting Norrie disease if their biological mother carries the mutated gene on one of two X chromosomes but doesn’t show signs of the condition. This happens because the gene on the other chromosome is sufficient for everything to function normally. A male baby can’t inherit the condition from their biological father.

How is Norrie disease diagnosed?

An ophthalmologist diagnoses Norrie disease by:

• Conducting a comprehensive eye exam and physical exam.
• Learning the medical history of your baby’s biological family.
• Ordering genetic testing.

Ophthalmologists must distinguish Norrie disease from other conditions that have similar signs, including:

• Retinoblastoma, in which a malignant tumor forms in the retina.
• Retinopathy of prematurity, in which the blood vessels that supply the retina aren’t fully developed.
• Persistent fetal vasculature.
• Coats disease.

There are other types of retinal disorders related to Norrie Disease and grouped under the rubric of familial exudative vitreoretinopathies. They’re generally milder and aren’t inherited in an X-linked fashion like Norrie disease.

Sometimes, diagnosis happens during pregnancy through amniocentesis. This may occur if there’s a family history of Norrie disease, or if the birth mother is a carrier of the NDP genetic mutation.

What is the treatment for Norrie disease?

Babies with Norrie disease need treatment tailored to their individual needs. Treatment options may include:

• Surgery. Surgery targets specific signs like cataracts. It can help prevent shrinking of a baby’s eyeballs and also ease pain. However, it can’t restore vision. Rarely, babies are born with attached retinas and can still perceive some light. In these cases, surgery may help these babies keep this ability.
• Hearing aids. Hearing aids help children, teens and adults hear sounds at louder volumes. They’re a vital link between a person with Norrie disease and the world around them.
• Cochlear implant. A cochlear implant helps people hear words and other sounds more clearly.

As your baby grows older, they’ll need continued care and monitoring by a team of healthcare professionals, including:

• Pediatricians.
• Geneticists.
• Ophthalmologists.
• Audiologists.
• Speech therapists.

Your child may also benefit from educational support services. It’s important to talk to administrators at your child’s school to learn what resources are available.

What is the outlook for people with Norrie disease?

Most people with Norrie disease experience total blindness (no light perception) within their first 12 months of life. About 1 in 5 people will be able to perceive some light after age 3.

Your child’s long-term outlook depends on many factors, including which features of the disease affect them and their severity. Your child’s team of healthcare providers is your best resource of information about ways Norrie disease may affect your child and how you can support their well-being.

Can I prevent Norrie disease?

You can’t prevent Norrie disease. If you have a family history of Norrie disease or other congenital eye diseases, you may want to consider genetic counseling prior to pregnancy. Your genetic counselor may advise genetic testing to determine if you’re carrying the NDP gene mutation. This mutation can lead to several different genetic eye diseases in your child, including Norrie disease.

How do I take care of my child?

Your child’s team of healthcare providers will tell you how best to care for your child at home. Each child’s needs vary based on their age and the features of the disease that affect them. Below is some general advice on how to help your child reach their fullest potential.

Take your child to appointments

Your child will have many appointments with healthcare providers from many different specialties. These appointments are essential for your child to receive care tailored to their individual needs. Appointments your child will need include:

• Eye checkups every 12 months. Annual appointments with an ophthalmologist are important even if your child has completely lost their vision. An ophthalmologist will check for any issues that might cause your child eye pain. They’ll suggest treatments if needed.
• Hearing checkups every six to 12 months. Regular monitoring of your child’s hearing allows them to receive timely treatment when needed. An audiologist will check for any signs of hearing loss before your child has symptoms. They’ll also check the progression of any existing hearing loss.
• Appointments to help your child’s development in other areas. Your child will meet with speech and language therapists, social workers, psychologists and others. The schedule will vary based on your child’s needs.
• Pediatrician appointments. Your child will need routine visits with a pediatrician to monitor their overall health. When your child is 12 to 14 years old, their pediatrician may begin planning their transition to adult primary care.

It’s important that all of your child’s providers collaborate with one another and share information. You may need to ask for such collaboration to happen and make sure that all providers are aware of any changes in your child’s health or needs.

Help your child manage daily life

Norrie disease poses challenges for many aspects of your child’s daily life. Your child may need help with:

• Sleeping and waking at regular times. Norrie disease can make it hard for your child to establish a healthy sleeping schedule. As a result, they may feel tired during the day, feel upset and struggle to focus on their schoolwork. If your child has trouble sleeping, talk to their pediatrician about strategies that can help.
• Socializing. As your child’s hearing loss progresses, they may find it challenging to play with other children or engage with the world around them. This can be especially noticeable during their teenage years. Your child may feel socially isolated or experience symptoms of depression. You can support your child by arranging social activities in quiet environments with low levels of background noise. This can help your child hear others more clearly and feel less stressed about communicating.
• Taking care of hearing aids. Your child’s hearing aids are a key part of treatment. But they may lose or damage these devices. It’s important to remember that caring for specialized medical equipment isn’t easy for any child. They may not realize the cost of this equipment, or the importance of taking good care of it. Norrie disease can pose additional challenges in this regard. As much as possible, help your child learn to take care of their hearing aids, and ask them to tell you right away if something happens to them.

Take care of yourself

Your child needs you to take care of yourself so you’re able to take care of them. It’s also essential to take care of yourself for your own sake. Burnout and exhaustion are common among parents and caregivers. There’s no easy fix, but acknowledging how you feel is the first step toward finding solutions. Here are some things you can do to help yourself:

• Talk to your healthcare provider about how you’re feeling. Feelings can include physical effects (such as exhaustion) and emotional effects (such as anxiety or depression). Your provider can recommend appropriate treatments or strategies to help.
• Join a support group. Ask your provider to recommend support groups or other resources to connect you with parents in similar situations. These can include parents of children with Norrie disease or other eye diseases. You may also find common ground with parents of children with other conditions that require close, daily care. The key is finding others who can relate to your situation, share their experiences and offer advice.
• Ask for help. Loved ones, neighbors and community groups may be able to help with tasks ranging from cooking meals to running errands. Build a group of trusted helpers who can support you and your family. This “village” can help your child feel supported and can be a vital lifeline for you as well.

What are other names for Norrie disease?

Other names for this condition include:

• Anderson-Warburg syndrome.
• Whitnall-Norman syndrome.
• Congenital progressive oculo-acoustico-cerebral degeneration.
• Oligophrenia microphthalmos.
• Pseudoglioma congenita.