Walker-Warburg syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Walker-Warburg syndrome is an inherited disorder that affects development of the muscles, brain, and eyes. It is the most severe of a group of genetic conditions known as congenital muscular dystrophies, which cause muscle weakness and wasting (atrophy) beginning very early in life. The signs and symptoms of Walker-Warburg syndrome are present at birth or in early infancy. Because of the severity of the problems caused by Walker-Warburg syndrome, most affected individuals do not survive past childhood.

Walker-Warburg syndrome affects the skeletal muscles, which are muscles the body uses for movement. Affected babies have weak muscle tone (hypotonia) and are sometimes described as "floppy." The muscle weakness worsens over time.

Walker-Warburg syndrome also affects the brain; individuals with this condition typically have a brain abnormality called cobblestone lissencephaly, in which the surface of the brain lacks the normal folds and grooves and instead develops a bumpy, irregular appearance (like that of cobblestones). These individuals may also have a buildup of fluid in the brain (hydrocephalus) or abnormalities of certain parts of the brain, including a region called the cerebellum and the part of the brain that connects to the spinal cord (the brainstem). These changes in the structure of the brain lead to significantly delayed development and intellectual disability. Some individuals with Walker-Warburg syndrome experience seizures.

Eye abnormalities are also characteristic of Walker-Warburg syndrome. These can include unusually small eyeballs (microphthalmia), enlarged eyeballs caused by increased pressure in the eyes (buphthalmos), clouding of the lenses of the eyes (cataracts), and problems with the nerve that relays visual information from the eyes to the brain (the optic nerve). These eye problems lead to vision impairment in affected individuals.

ORPHANET DEFINITION A rare form of congenital muscular dystrophy (CMD) associated with severe brain and eye abnormalities. It is the most severe form of CMD.

Causes

From: MedlinePlus Genetics, National Library of Medicine

Because of the severity of the problems caused by Walker-Warburg syndrome, most affected individuals do not survive past childhood. These can include unusually small eyeballs (microphthalmia), enlarged eyeballs caused by increased pressure in the eyes (buphthalmos), clouding of the lenses of the eyes (cataracts), and problems with the nerve that relays visual information from the eyes to the brain (the optic nerve).

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Point prevalence: <1 / 1 000 000; United Kingdom; Value and class. Prevalence at birth: 1-9 / 100 000; Europe; Value and class. Point prevalence: 1-9 / 1 000 000; Europe; Class only. Prevalence at birth: 1-9 / 100 000; Italy; Value and class.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal aldolase level · Very frequent (99-80%)

An abnormal concentration of aldolase in the serum. Aldolase is an enzyme responsible for converting fructose 1,6-bisphosphate into the triose phosphates dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.

Abnormal circulating creatine kinase concentration · Very frequent (99-80%)

Any deviation from the normal activity of creatine kinase in the blood circulation.

Abnormal cortical gyration · Very frequent (99-80%)

An abnormality of the gyri (i.e., the ridges) of the cerebral cortex of the brain.

Abnormal lactate dehydrogenase activity · Very frequent (99-80%)

A deviation from the normal serum concentration/activity of lactate dehydrogenase (LDH), which catalyzes the reduction of pyruvate to form lactate.

Abnormal optic nerve morphology · Very frequent (99-80%)

Abnormality of the optic nerve.

Abnormality of neuronal migration · Very frequent (99-80%)

An abnormality resulting from an anomaly of neuronal migration, i.e., of the process by which neurons travel from their origin to their final position in the brain.

Abnormality of the cerebellar vermis · Very frequent (99-80%)

An anomaly of the vermis of cerebellum.

Aplasia/Hypoplasia involving the skeletal musculature · Very frequent (99-80%)

Absence or underdevelopment of the musculature.

Areflexia · Very frequent (99-80%)

Absence of neurologic reflexes such as the knee-jerk reaction.

Cerebellar hypoplasia · Very frequent (99-80%)

Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.

Chorioretinal dysplasia · Very frequent (99-80%)

Abnormal development of the choroid and retina.

Global developmental delay · Very frequent (99-80%)

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

Hydrocephalus · Very frequent (99-80%)

Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.

Hyporeflexia · Very frequent (99-80%)

Reduction of neurologic reflexes such as the knee-jerk reaction.

Other findings in the same source

From: Orphanet

Additional reported features include Hypotonia (Very frequent (99-80%)); Intellectual disability (Very frequent (99-80%)); Lissencephaly (Very frequent (99-80%)); Metatarsus valgus (Very frequent (99-80%)); Muscle weakness (Very frequent (99-80%)); Muscular dystrophy (Very frequent (99-80%)); Optic atrophy (Very frequent (99-80%)); Pachygyria (Very frequent (99-80%)); Pachygyria (Very frequent (99-80%)); Polymicrogyria (Very frequent (99-80%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Antenatal; Infancy; Neonatal

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Point prevalence: <1 / 1 000 000; United Kingdom; Value and class. Prevalence at birth: 1-9 / 100 000; Europe; Value and class. Point prevalence: 1-9 / 1 000 000; Europe; Class only. Prevalence at birth: 1-9 / 100 000; Italy; Value and class.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Walker-Warburg syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Walker-Warburg syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.