Walker-Warburg Syndrome

What is Walker-Warburg syndrome?

Walker-Warburg syndrome is a genetic condition that affects the muscles in your child’s body, including their brain and their eyes. This condition is a type of congenital muscular dystrophy present at birth or infancy that leads to progressive muscle weakness over time. This condition causes life-threatening symptoms for children and a shortened life expectancy.

What is dystroglycanopathy?

You might hear Walker-Warburg syndrome identified as dystroglycanopathy. Walker-Warburg syndrome is a form of congenital (appears at birth) muscular dystrophy, which is a group of conditions that target the muscles of your child’s body. There are several types of muscular dystrophy categorized as dystroglycanopathy, which identifies forms of muscular dystrophy caused by genes that produce the dystroglycan protein. Walker-Warburg syndrome is the most severe type of dystroglycanopathy.

How common is Walker-Warburg syndrome?

Walker-Warburg syndrome affects a worldwide estimate of 1 in every 60,500 newborns. This condition can affect anyone since it’s the result of a genetic mutation.

Can my child inherit Walker-Warburg syndrome?

Yes, your child can inherit Walker-Warburg syndrome. The condition passes from both parents to a child during conception when both parents are carriers of one of the mutated genes that cause Walker-Warburg syndrome. When both parents pass the gene onto their child, the condition is autosomal recessive. If your child only receives one copy of the mutated gene from one parent, your child won’t experience symptoms but will be a carrier of the condition.

How does Walker-Warburg syndrome affect my child’s body?

Walker-Warburg syndrome affects the muscles in your child’s body. You’ll notice symptoms that affect your child’s muscles when they’re born because they’ll appear “floppy” since their muscle tone is weak. Beyond their muscles, this condition can affect how your child’s brain and eyes form and function. Your child might have a visual impairment, developmental delays and problems with cognitive development. Treatment focuses on managing these symptoms to prevent a shortened life expectancy.

What are the symptoms of Walker-Warburg syndrome?

Walker-Warburg syndrome causes symptoms that affect your child’s muscles, brain and eyes. Symptoms range in severity and are usually present at birth or early infancy. Symptoms can be life-threatening.

Muscle symptoms

Symptoms of Walker-Warburg syndrome affect the muscles that your child uses for movement. When your baby is born, they might appear “floppy” like a rag doll because of their weak muscle tone (hypotonia). Babies with hypotonia have trouble lifting their head, arms and legs. The condition weakens your child’s muscles progressively, which means their symptoms will worsen over time.

Since your baby’s muscles don’t work as they should, they could have trouble feeding during early infancy.

Brain symptoms

Walker-Warburg syndrome affects how your child’s brain develops. Symptoms that affect your child’s brain could include:

• Their brain appears bumpy and doesn’t have folds or grooves (lissencephaly).
• Fluid buildup in their brain (hydrocephalus).
• Growth abnormalities at their brainstem and cerebellum or a cyst in their cerebellum (Dandy-Walker malformation).
• Seizures.

Symptoms that affect your child's brain can lead to delayed development and challenges with intellectual abilities.

Eye symptoms

Walker-Warburg syndrome can affect the development of your child’s eyes and cause symptoms including:

• Small eyeballs (microphthalmia) or large eyeballs (buphthalmos).
• Cloudy eyes (cataracts).
• Delay between nerves that send messages from their eyes to their brain (optic nerves).
• Difficulty seeing clearly (vision impairment).

What causes Walker-Warburg syndrome?

A genetic mutation causes Walker-Warburg syndrome. There are more than a dozen genes that cause the condition and many more which haven’t been identified yet. Genetic mutations that cause more than half of all Walker-Warburg syndrome cases include:

• POMT1.
• POMT2.
• CRPPA.
• FKTN.
• FKRP.
• LARGE1.
• POMGNT1.
• ISPD.
• GTDC2.
• DAG1.

The genes that cause Walker-Warburg syndrome disrupt glycosolation of α-dystroglycan. Without this glycosolation process, your child’s muscle fibers can’t maintain their structure within their body. These proteins also affect nerve cell movement in their brain during fetal development, leading to lissencephaly.

If your child is diagnosed with Walker-Warburg syndrome, their muscles contract (tighten) and relax (loosen) too often. Over time, their muscle fibers become too damaged to function by making them weak.

In addition, Walker-Warburg syndrome disrupts the traffic of the neurons in their brain. When neurons reach their destination, they’re supposed to stop. Instead, neurons affected by Walker-Warburg syndrome keep moving into the fluid that surrounds your child's brain.

How is Walker-Warburg syndrome diagnosed?

Your healthcare provider will begin the diagnosis of Walker-Warburg syndrome during the late stages of pregnancy and confirm the diagnosis once your child is born. An ultrasound can detect symptoms during pregnancy, especially symptoms that affect your child's brain. Imaging tests (radiology), like a CT scan and an MRI, are also helpful to get a clear image of your child’s brain once they’re born.

Several tests confirm a diagnosis of Walker-Warburg syndrome, including:

• A muscle tissue biopsy to see if your child’s muscle fibers are healthy.
• A blood test to identify creatine kinase (CK) levels, which is the breakdown of muscle tissue in your child’s body. A high CK test confirms muscle damage.
• An eye exam to look for symptoms of Walker-Warburg syndrome in your child's eyes.
• A genetic blood test to identify the mutated gene that causes symptoms.

How is Walker-Warburg syndrome treated?

Since there's no cure for Walker-Warburg syndrome, treatment focuses on alleviating symptoms. Treatment is unique to each child diagnosed with the condition and could include:

• Undergoing surgery to remove excess fluid from their brain (hydrocephalus).
• Taking medicine to prevent seizures.
• Participating in physical therapy to improve muscle strength.
• Inserting a feeding tube to help with feeding difficulties.

Treatment for Walker-Warburg syndrome aims to prevent life-threatening symptoms to improve your child’s life expectancy.

How can I prevent Walker-Warburg syndrome?

Since Walker-Warburg syndrome is a genetic condition, there's no way to prevent it. If you plan on becoming pregnant and want to understand your risk of having a child with a genetic condition, talk to your healthcare provider about genetic testing or genetic counseling.

What can I expect if my child has Walker-Warburg syndrome?

Walker-Warburg syndrome is a progressive condition that causes symptoms to start mild but get worse over time. This means that babies diagnosed with this condition have a short life expectancy into early childhood. Your child’s healthcare provider will offer treatment to prevent life-threatening symptoms and prolong your child’s life. There is no cure for Walker-Warburg syndrome.

During your child’s diagnosis, it’s important to take care of yourself too. It might be beneficial to talk to a genetic counselor to help you and your family navigate your child’s diagnosis and treatment options. A mental health professional can help you prepare and adapt to the sudden loss of your child due to their diagnosis. Bereavement and support groups provide comfort to families during a difficult loss.

When should my child see their healthcare provider?

Contact your child's healthcare provider if your child experiences symptoms of Walker-Warburg syndrome, especially if they’re unable to eat. Also contact them if your child has success with treatment to alleviate symptoms but their symptoms unexpectedly reappear or get worse.

Your child is at risk of having seizures. If you notice your child loses consciousness temporarily, shakes or moves uncontrollably, or appears confused, frightened or anxious, visit the emergency room.

What questions should I ask my child's healthcare provider?

• Does my child need surgery?
• What are the side effects of treatment?
• What do I do if my child has a seizure?
• How often does my child need to have wellness checkups?

A note from Cleveland Clinic

It can be devastating to learn that your newborn has a congenital condition that can prevent them from living a full life. During this challenging diagnosis, your healthcare provider will offer treatment to prevent life-threatening symptoms and to prolong your child’s life expectancy. Your child’s diagnosis will likely take a toll on you and your family, so make sure you find the care you need. Many people find genetic counseling beneficial to learn more about how they can care for their child. A mental health specialist can help you navigate stress, prepare and cope after an unexpected loss. Surround yourself with support, and talk with your provider if you need help.