Walker-Warburg Syndrome

Walker-Warburg Syndrome (WWS) is a rare genetic disorder that belongs to a group of diseases known as congenital muscular dystrophies. It is characterized by muscle weakness, brain and eye abnormalities, and other developmental defects. WWS is considered the most severe form of congenital muscular dystrophy and is often fatal in the early years of life.

Causes

WWS is caused by mutations in several genes involved in the glycosylation of dystroglycan, a protein essential for the stability and integrity of muscle cells and for the normal development of the brain and eyes. The most commonly implicated genes include POMT1, POMT2, FKRP, FKTN, LARGE, and others. These genetic mutations are inherited in an autosomal recessive manner, meaning that a child must inherit two copies of the mutated gene, one from each parent, to be affected.

Symptoms

The symptoms of Walker-Warburg Syndrome are present at birth and can include:

• Muscle weakness and hypotonia (reduced muscle tone)
• Severe brain malformations, such as lissencephaly (smooth brain), cerebellar hypoplasia (underdeveloped cerebellum), and hydrocephalus (excess fluid in the brain)
• Eye defects like cataracts, microphthalmia (abnormally small eyes), or buphthalmos (enlarged eyes due to increased pressure)
• Intellectual disability
• Seizures
• Facial abnormalities

Diagnosis

Diagnosis of Walker-Warburg Syndrome is based on clinical examination, imaging studies such as MRI of the brain, and genetic testing. Prenatal diagnosis is possible through genetic testing if there is a known family history of the disease.

Treatment

There is no cure for WWS, and treatment is supportive and symptomatic. Management may include:

• Physical therapy to improve muscle strength and mobility
• Treatment of seizures with antiepileptic drugs
• Management of hydrocephalus, often requiring surgical intervention
• Monitoring and treatment of eye abnormalities
• Supportive care for feeding and respiratory difficulties

Prognosis

The prognosis for individuals with Walker-Warburg Syndrome is poor, with most affected children not surviving beyond the age of three years due to complications related to brain abnormalities, respiratory infections, or other associated health issues.

Research

Research efforts are ongoing to better understand the genetic causes of WWS and to develop potential therapies. Studies are focused on the role of dystroglycan in muscle and brain development and on finding ways to correct the underlying genetic defects.