Walker-Warburg Syndrome- Causes, Symptoms, Diagnosis, and Treatment.

Introduction:

Walker-Warburg Syndrome is a kind of congenital muscular dystrophy (muscle weakness disorders present at birth) that has an onset at birth or in infancy and results in progressive muscle weakness over time. This condition is life-threatening, and children suffering from this condition have a shortened life expectancy. The majority of children with Walker-Warburg Syndrome do not survive past 3 years of age.

Is Walker-Warburg Syndrome Common?

About 1 in 60,500 newborn babies are affected by Walker-Warburg Syndrome. The condition has no predeliction and anyone can be affected as it occurs due to genetic mutation.

What Are the Causes of Walker-Warburg Syndrome?

A genetic mutation is responsible for causing Walker-Warburg Syndrome. More than a dozen genes are involved in causing the mutation, and many more remain unknown. The following are some of the known genes that cause genetic mutations:

• POMT1.

• POMT2.

• CRPPA 1.

• FKTN.

• FKRP.

• LARGE1.

• POMGNT1.

• ISPD.

• GTDC2.

• DAG1.

Genetic mutations occur in the following ways:

• A protein called alpha-dystroglycan is responsible for anchoring the structural framework inside a cell called the cytoskeleton with the lattice of proteins and other molecules present on the exterior extracellular matrix.

• This anchoring function of glycosylated alpha-dystroglycan provides stability and protects the skeletal muscle fibers.

• Its function in the brain is to facilitate the movement of nerve cells called neurons during early development.

• The genetic mutations hinder the glycosylation of alpha-dystroglycan and affect their normal function. Since the stability of the muscle cells is affected due to the lack of functional alpha-dystroglycan, muscle fibers get damaged as they are subjected to repeated contraction and relaxation with use.

• The damaged fibers weaken and die after a particular period resulting in progressive weakness of the skeletal muscles.

• Defective glycosylation of alpha-dystrogly can also influences the migration of neurons during the initial stages of brain development. During development, the neurons in this condition migrate past the brain's surface and traverse into the surrounding fluid-filled spaces. Researchers consider this issue with neuronal migration to cause cobblestone lissencephaly (the brain is devoid of the usual grooves and folds, creating a cobblestone appearance called smooth brain) in kids with Walker-Warburg syndrome.

• The impact of gene mutations on other parts of the body, like the eyes, is not entirely known.

Since this syndrome has a malfunction of alpha-dystroglycan, Walker-Warburg Syndrome is classified as dystroglycanopathy.

How Does a Child Inherit Walker-Warburg Syndrome?

If both parents carry one of the mutated genes that cause Walker-Warburg Syndrome and pass the gene to the child, it is called autosomal recessive. On the contrary, if the child receives only a single copy of the mutated gene from one parent, the child will be a carrier of the condition and will not experience any symptoms.

What Are the Symptoms of Walker-Warburg Syndrome?

The following are the symptoms of Walker-Warburg Syndrome:

• Babies appear ‘floppy’ due to weak muscle tone (hypotonia). These babies have difficulty raising their heads, arms, and legs.

• Difficulty feeding during early infancy since the muscles do not function properly.

• Hydrocephalus (fluid buildup in the brain).

• Growth abnormalities present in the brainstem or cerebellum or the presence of a cyst in the cerebellum (Dandy-Walker malformation).

• Absence of folds or grooves in the brain which makes it appear bumpy (lissencephaly) during diagnosis.

• Seizures (sudden, uncontrolled body movements along with changes in behavior due to abnormal electrical activity in the brain).

• Since the brain is affected, there will be delayed development and problems with intellectual abilities.

• Small eyeballs (microphthalmia) or large eyeballs (buphthalmos).

• Cataracts (cloudy eyes).

• Vision impairment (difficulty in seeing clearly).

• Optic nerve delay (delay in sending messages from the nerves of the eyes to the brain).

How Can Walker-Warburg Syndrome Be Diagnosed?

Walker-Warburg Syndrome can be diagnosed during pregnancy in the following ways:

• The diagnosis begins in late pregnancy and is confirmed after the delivery of the child.

• Ultrasound is effective in identifying any symptoms that affect the child’s brain.

• Other imaging tests include CT (computed tomography) and MRI (magnetic resonance imaging) scans.

The following are the diagnostic methods after the baby is born.

• A muscle tissue biopsy helps evaluate whether the baby’s muscle fibers are healthy.

• A blood test is taken to estimate creatinine kinase (CK) levels which denotes the breakdown of muscle tissue in the child’s body. A high CK test confirms the diagnosis of Walker-Warburg Syndrome.

• An eye examination is done to check for associated symptoms in the child’s eyes.

• A genetic blood test may be carried out to detect the mutated gene that causes the symptoms.

Can Walker-Warburg Syndrome Be Treated?

There is no cure for Walker-Warburg Syndrome. However, the symptoms can be managed in the following ways:

• Surgery to remove excess fluid in the brain (hydrocephalus).

• Medications to prevent seizures.

• Physical therapy exercises to promote muscle strength.

• Inserting a feeding tube to cope with feeding difficulties.

Can Walker-Warburg Syndrome Be Prevented?

Since the condition is hereditary, it cannot be prevented. The person who is planning to become pregnant and would like to know the risk of giving birth to a child with a genetic condition can discuss genetic testing or genetic counseling with their physician.

What Is the Prognosis of a Child With Walker-Warburg Syndrome?

The condition gradually sets in with mild symptoms that can worsen with time. These babies have a short life expectancy and mostly do not get through early childhood. A physician can provide treatment to prevent life-threatening symptoms and prolong the child's life expectancy to a certain extent but cannot offer a permanent cure. One can consult a genetic counselor to get advice on the child’s diagnosis and treatment options. The child’s parents and family can undergo sessions with a mental health professional to cope with the child’s fatal condition.

Conclusion:

Walker-Warburg Syndrome is a rare genetic disorder that causes muscle weakness and muscle wasting called atrophy in the early stages of life. The symptoms manifest at birth or during early infancy. The body's skeletal muscles are affected, and muscle weakness worsens with time. Since the problems associated with this condition are severe, most of the affected children do not live beyond three years of age.