What Is Walker-Warburg Syndrome?
Walker-Warburg Syndrome is an extremely rare pathological genetic condition which affects multiple organ systems of the body to include the brain, muscles, and the eyes. This disease is characterized by smooth appearance of the brain surface with lack of the normal folding and malformations of other structures of the brain to include the cerebellum and the brainstem.
A child with Walker-Warburg Syndrome will also have severe ocular abnormalities with partial to complete blindness. Additionally, children with Walker-Warburg Syndrome will have progressive weakness of the voluntary muscles of the body. This condition is called as congenital muscular dystrophy.
A child with Walker-Warburg Syndrome is unable to survive for more than one year of life in majority of the cases even though the symptoms may be variable and differ on a case to case basis.
Walker-Warburg Syndrome follows an autosomal recessive pattern of inheritance meaning that two copies of the defective gene one from each parent is required for a child to develop Walker-Warburg Syndrome.
What Are The Causes Of Walker-Warburg Syndrome?
Walker-Warburg Syndrome is basically caused by faulty genes that cater to normal functioning of the brain, eyes, and the muscles of the body. As stated, it follows an autosomal recessive pattern meaning that two copies of the defective gene one from each parent is required for development of this condition.
Due to the defective gene, there is complete lack of proteins that are extremely vital for proper normal development and functioning of the brain, eyes, and muscles. These protein works in tandem with another protein called the α-dystroglycan. This protein is found in the membranes of muscle and nerve cells.
This protein facilitates stabilization of the muscle cells and aid in migration of the nerve cells in the brain during development. The proteins that cause Walker-Warburg Syndrome are required for attachment of the sugar molecules to α-dystroglycan. This process is called as glycosylation.
Glycosylation is extremely necessary for α-dystroglycan to function normally. If any of the genes that are responsible for encoding of any of the proteins responsible for Walker-Warburg Syndrome gets mutated then the glycosylation does not take place normally resulting in the development of Walker-Warburg Syndrome.
There are at least 14 genes as of now that have been related to Walker-Warburg Syndrome. These genes are B3GALNT2, B4GAT1, DAG1, FKRP, FKTN, GMPPB, ISPD, LARGE, POMT1, POMT2, POMGNT1, POMGNT2, POMK, and TMEM5. Mutation in any of these genes results in the development of Walker-Warburg Syndrome.
What Are The Symptoms Of Walker-Warburg Syndrome?
The classic presenting feature of Walker-Warburg Syndrome is the presence of abnormalities in the brain and eyes. Children with Walker-Warburg Syndrome will also have congenital muscular dystrophy with gradual degeneration and weakness of the voluntary muscles of the body.
As a result of the muscular dystrophy, the child will have severe hypotonia of the muscles. This muscles weakness gradually worsens as the disease condition advances. Joint contractures are also seen in some cases of Walker-Warburg Syndrome.
Regarding abnormality in the brain, the normal folds of the brain are missing in children with Walker-Warburg Syndrome. Hydrocephalus is also seen in children with Walker-Warburg Syndrome.
Underdevelopment of the cerebellum and brainstem is also in Walker-Warburg Syndrome resulting incoordinated voluntary muscle movements which is controlled by the cerebellum. Breathing and salivation also gets affected as these are controlled by the brainstem.
Ocular abnormalities which are seen in children with Walker-Warburg Syndrome can include abnormally small eyes, absence of the optic nerve, retinal malformations resulting in retinal detachment.
Formation of cataracts and development of glaucoma can also be seen in individuals with Walker-Warburg Syndrome. Almost all of these abnormalities lead to partial of complete blindness in the child with Walker-Warburg Syndrome.
If a child survives this disease past one year of life then even while growing he or she will have significant delays in reaching their milestones. They will have significant learning disability.
They may also have problems with breathing and swallowing as a result of Walker-Warburg Syndrome. In some cases urinary blockage has also been noted in children with Walker-Warburg Syndrome along with inability of the testes to descend into the scrotum in males due to Walker-Warburg Syndrome.
How Is Walker-Warburg Syndrome Diagnosed?
A prenatal ultrasound can detect the presence of Walker-Warburg Syndrome in late pregnancies. The diagnosis can be confirmed at birth with the characteristic findings of Walker-Warburg Syndrome.
The abnormalities in the brain can be clearly seen on an MRI or CT scan of the brain. Once suspected, a genetic testing will clearly show mutation in the genes responsible for causing this condition and confirm the diagnosis of Walker-Warburg Syndrome.
How Is Walker-Warburg Syndrome Treated?
As of now, there is no treatment for Walker-Warburg Syndrome. In majority of the cases, a child is not able to survive more than a year of life with this condition. The treatment is purely symptomatic and supportive.
The treatment will require combined efforts of a team of physicians comprising of pediatrics, orthopedics, ophthalmologists, and neurologists who can formulate a comprehensive treatment plan for the child with Walker-Warburg Syndrome.
Seizures caused due to this condition can be treated with anticonvulsants whereas surgery may be required to treat conditions like hydrocephalus. Aggressive physical therapy will be needed for improvement of muscle strength.
For feeding and swallowing difficulties an NG tube may be placed. Despite all the efforts, the overall prognosis is rather poor for a child suffering from Walker-Warburg Syndrome.