Walker–Warburg syndrome

Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
Founder, WikiMD Wellnesspedia &
W8MD medical weight loss NYC and sleep center NYC

Other Names

• Hydrocephalus, agyria and retinal dysplasia; Hard syndrome; Hard +/- E syndrome; See More

• This disease is grouped under: Congenital disorder of glycosylation with developmental anomaly; Congenital muscular alpha-dystroglycanopathy with brain and eye anomalies; Congenital muscular dystrophy; See More

Clinical features

• Walker-Warburg syndrome (WWS) is a severe form of congenital muscular dystrophy associated with brain and eye abnormalities. Signs and symptoms are typically present at birth and include hypotonia, muscle weakness, developmental delay, intellectual disability and occasional seizures. It is also associated with lissencephaly, hydrocephalus, cerebellar malformations, eye abnormalities, and other abnormalities. Most children do not survive beyond the age of three years. It may be caused by mutations in any of several genes including the POMT1, POMT2 and FKRP genes, although in many individuals the genetic cause is unknown.

Inheritance

WWS is inherited in an autosomal recessive manner.

Diagnosis

Laboratory investigations usually show elevated creatine kinase, myopathic/dystrophic muscle pathology and altered α-dystroglycan. Antenatal diagnosis is possible in families with known mutations. Prenatal ultrasound may be helpful for diagnosis in families where the molecular defect is unknown.

Symptoms

80%-99% of people have these symptoms

• Abnormal aldolase level
• Abnormal circulating creatine kinase concentration
• Abnormal lactate dehydrogenase level
• Aplasia/Hypoplasia involving the skeletal musculature
• Areflexia
• Cerebellar hypoplasia
• Chorioretinal dysplasia
• Global developmental delay
• Hydrocephalus
• Hyporeflexia
• Intellectual disability
• Macrogyria
• Metatarsus valgus
• Muscle weakness
• Muscular dystrophy
• Muscular hypotonia
• Optic atrophy
• Pachygyria
• Polymicrogyria
• Retinal detachment
• Retinal dysplasia
• Retinal dystrophy
• Skeletal muscle atrophy
• Specific learning disability

30%-79% of people have these symptoms

• Absent septum pellucidum
• Agenesis of corpus callosum
• Anophthalmia
• Corneal opacity
• Cryptorchidism
• Dandy-Walker malformation
• Glaucoma
• Hypoplasia of penis
• Macrocephaly
• Microphthalmia

5%-29% of people have these symptoms

• Bifid uvula
• Cataract
• Iris coloboma
• Low-set ears
• Microcephaly
• Microcornea
• Posteriorly rotated ears
• Protruding ear
• Seizure
• Submucous cleft hard palate

Uncommon symptoms

• Agyria
• Anal atresia
• Atresia of the external auditory canal
• Autosomal recessive inheritance
• Blindness
• Buphthalmos
• Cerebellar dysplasia
• Cleft palate
• Cleft upper lip
• Coloboma
• Congenital contracture
• Congenital muscular dystrophy
• Elevated serum creatine kinase
• Excessive daytime somnolence
• Hypoplasia of the brainstem
• Hypoplasia of the corpus callosum
• Hypoplastic male external genitalia
• Intellectual disability
• Megalocornea
• Meningoencephalocele
• Microtia
• Myopia
• Occipital encephalocele
• Optic nerve hypoplasia
• Peters anomaly
• Posterior fossa cyst
• Renal dysplasia
• Retinal atrophy
• Severe muscular hypotonia
• Type II lissencephaly

Treatment

• There is currently no cure or treatment for Walker-Warburg syndrome.
• Management is generally only supportive and preventive.
• Individuals who develop seizures are typically treated with anticonvulsants.
• A few children require surgical procedures, such as shunting for hydrocephalus or correction of encephalocele.
• Physical therapy can be offered to aid in development or prevent worsening of contractures
• Feeding usually needs to be monitored and in some cases, a supplemental nasogastric or gastric feeding tube may be necessary.

Prognosis

• No specific treatment is available. Management is only supportive and preventive.
• Those who are diagnosed with the disease often die within the first few months of life. Almost all children with the disease die by the age of three.

Eponym

• WWS is named for Arthur Earl Walker and Mette Warburg (1926-2015), a Danish Ophthalmologist.

Latest research

• Most recent articles
• Ongoing trials

Walker–Warburg syndrome Resources
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NIH genetic and rare disease info

• NIH info on Walker–Warburg syndrome

Walker–Warburg syndrome is a rare disease.