Walker-Warburg Syndrome

What is Walker Warburg Syndrome?

Walker Warburg syndrome, a genetic disorder that affects the brain, eyes, and muscles, is a type of congenital muscular dystrophy seen at birth or during infancy, leading to progressive muscle weakness over time. This syndrome results in symptoms that threaten the child’s life and reduce life expectancy.

In some cases, Walker Warburg syndrome is also referred to as dystroglycanopathy. It is a type of congenital muscular dystrophy that targets the muscles in the child’s body. There are several forms of muscular dystrophy categorized under dystroglycanopathy, caused by mutations in genes producing the dystroglycan protein. Walker Warburg is the most severe disease in this group.

Causes of Walker Warburg Syndrome

Walker Warburg syndrome is caused by genetic mutations, with over a dozen known mutations linked to the syndrome. Additionally, it is believed that more unidentified gene mutations may contribute to the syndrome. Mutations that cause the condition and affect more than half of the cases include:

• GTDC2
• ISG
• POMGNT1
• BIG1
• FKRP
• FKTN
• POMT2
• POMT1
• DAG1

Mutations causing Walker Warburg syndrome disrupt the glycosylation of a-dystroglycan. Without this glycosylation process, the child’s muscle fibers cannot maintain their structure. These proteins also affect neuronal movement in the brain during fetal development, leading to lissencephaly.

When a child is diagnosed with Walker Warburg syndrome, frequent muscle spasms occur, leading to damage in muscle fibers, which eventually weaken and lose their function.

Additionally, the syndrome disrupts neuron traffic in the brain. When neurons reach their targets, they should stop, but affected neurons continue moving towards the surrounding fluid in the brain.

Symptoms of Walker Warburg Syndrome

This syndrome affects the eyes, brain, and muscles of the child, resulting in symptoms in these areas. Symptoms vary depending on the severity of the disease but typically appear at birth or during infancy. These symptoms can endanger the child's life.

Muscle Symptoms

The syndrome affects the muscles that enable the baby to move, resulting in weak muscle tone at birth, a condition known as hypotonia. Babies with hypotonia appear limp like ragdolls. Babies with hypotonia have difficulty lifting their heads, arms, and legs. As the disease progresses, the child’s muscles weaken further. This causes worsening symptoms over time, and babies may experience feeding problems due to the muscles not functioning properly during infancy.

Brain Symptoms

Walker Warburg syndrome also affects the brain development of children. Symptoms affecting the brain include:

• The brain appears bumpy with no folds or grooves.
• Fluid accumulation in the brain.
• Abnormal growth in the brainstem and cerebellum.
• Cysts in the cerebellum.
• Seizures.

The symptoms affecting the brain lead to poor brain development and difficulty in cognitive abilities.

Eye Symptoms

The syndrome can also affect the eyes of children. Symptoms in the eyes may include:

• Small or large pupils.
• Blurred vision.
• Delayed optic nerve function.
• Difficulty seeing clearly.

Diagnosis Criteria for Walker Warburg Syndrome

The initial diagnosis of Walker Warburg syndrome can be made during the late stages of pregnancy with ultrasound imaging. However, definitive diagnosis is made after birth using imaging tests. Tests for confirming the syndrome include:

• Muscle biopsy to assess the child’s muscle condition.
• Blood tests to determine creatine kinase levels, which indicate muscle damage.
• Eye examination.
• Genetic testing to identify the gene causing the symptoms.

Treatment Methods for Walker Warburg Syndrome

There is no cure for Walker Warburg syndrome. Treatments are aimed at alleviating symptoms. Since each child’s needs are unique, individualized treatment plans are created. Possible treatments include:

• Surgical intervention to remove excess fluid in the brain.
• Medication to prevent seizures.
• Physical therapy to increase muscle strength.
• Insertion of a feeding tube to address feeding difficulties.

Living with Walker Warburg Syndrome

The symptoms seen in babies born with this syndrome are progressive, and therefore, most children have a short life expectancy, typically into early childhood. Various methods can be used to extend the child’s life expectancy, but there is no cure to fully resolve the syndrome.

Parents caring for a child with this condition must also take care of themselves and seek psychological counseling if necessary. Support from family and friends is also crucial.

If symptoms are noticed, especially feeding issues, it is essential to consult a specialist and begin treatment to manage the symptoms. Symptoms may temporarily disappear but will likely return and worsen. In this case, further consultation with a doctor is required.

Children are at risk of seizures. If a child temporarily loses consciousness, trembles, moves uncontrollably, appears confused, frightened, or anxious, emergency medical assistance should be sought.

Risk Factors for Walker Warburg Syndrome

Walker Warburg syndrome is inherited through genetic mutations, passed down from parents who carry the mutated genes. If both parents are carriers, the child will develop the disease, a condition known as autosomal recessive inheritance. If only one parent has the mutated gene, the child will be a carrier but will not show symptoms.