WWS; WWS Muscular Dystrophy; Warburg syndrome; Pagon Syndrome; Chemke Syndrome; Hydrocephalus, Agyria and Retinal Dysplasia; HARD +/- Syndrome; HARDE syndrome; Muscle-Eye-Brain disease; Cerebro-oculomuscular syndrome; Lissencephaly type II; Oculocerebral malformation

Walker Warburg Syndrome (WWS) is a rare form of autosomal recessive CMD and is the most severe type of CMD. WWS is present at birth and results in fatal neurological lesions in the brain that are characterized by smoothness of the surface of the brain, thickening of the cortex and other brain abnormalities. Several genetic mutations occur in WWS: POMT1, POMT2 and fukutin protein.

Diagnostic testing: Laboratory tests showing elevated creatine kinase (CK), myopathic/dystrophic muscle pathology and altered a-dystroglycan. EMG showing myopathic changes in the brain. Genetic testing is definitive.

Physical findings: Symptoms include:

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  Hypotonia (weak muscle tone);

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  Muscle weakness;

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  Developmental delay with intellectual disability;

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  Occasional seizures;

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  Eye abnormalities (retinal detachment, cataracts, conjunctivitis) which lead to blindness;

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  Encephalocele; and

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  Cleft lip and cleft palate.

ICD-9: 359.0

WWS is the most severe form of the CMD with most children dying before age three. The few children who survive until 5 years of age have severe intellectual disability and delayed development.

There is currently no cure for Walker Warburg Syndrome. Supportive care is the only form of treatment currently available.

SUGGESTED PROGRAMMATIC ASSESSMENT*

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  Clinical examination including a description of physical findings;

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  Family history;

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  Genetic testing;

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  Electromyography or nerve conduction tests; and

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  Blood and enzyme tests.

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