Walker–Warburg syndrome (WWS), also called Warburg syndrome, Chemke syndrome, HARD syndrome (Hydrocephalus, Agyria and Retinal Dysplasia), Pagon syndrome, cerebroocular dysgenesis (COD) or cerebroocular dysplasia-muscular dystrophy syndrome (COD-MD), is a rare form of autosomal

Autosome

An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...

 recessive congenital

Congenital disorder

A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...

 muscular dystrophy

Muscular dystrophy

Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...

. It is associated with brain (lissencephaly

Lissencephaly

Lissencephaly, which literally means smooth brain, is a rare brain formation disorder caused by defective neuronal migration during the 12th to 24th weeks of gestation, resulting in a lack of development of brain folds and grooves . It is a form of cephalic disorder...

, hydrocephalus

Hydrocephalus

Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...

, cerebellar malformations) and eye

Human eye

The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...

 abnormalities. This condition has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years.

Characteristics

The clinical manifestations present at birth are generalized hypotonia

Hypotonia

Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...

, muscle weakness, developmental delay with mental retardation

Mental retardation

Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...

 and occasional seizures. The congenital muscular dystrophy is characterized by hypoglycosylation of α-dystroglycan.

Cause and Genetics

Several genes have been implicated in the etiology of Walker–Warburg syndrome, and others are as yet unknown. Several mutations were found in the protein O-Mannosyltransferase POMT1

POMT1

Protein O-mannosyl-transferase 1 is an enzyme that in humans is encoded by the POMT1 gene. It is a member of the dolichyl-phosphate-mannose-protein mannosyltransferases.- Function :...

 and POMT2

POMT2

Protein O-mannosyl-transferase 2 is an enzyme that in humans is encoded by the POMT2 gene.- Function :POMT2 encodes an integral membrane protein of the endoplasmic reticulum that shares significant sequence similarity with a family of protein O-mannosyltransferases of S. cerevisiae...

 genes, and one mutation was found in each of the fukutin

Fukutin

Fukutin is a eukaryotic protein necessary for the maintenance of muscle integrity, cortical histogenesis, and normal ocular development. Mutations in the fukutin gene have been shown to result in Fukuyama congenital muscular dystrophy characterised by brain malformation - one of the most common...

 and fukutin-related protein

Fukutin-related protein

Fukutin-related protein is a protein associated with congenital muscular dystrophy.-External Links:* * LOVD mutation database:...

 genes.

Diagnosis

Laboratory investigations usually show elevated creatine kinase

Creatine kinase

Creatine kinase , also known as creatine phosphokinase or phospho-creatine kinase , is an enzyme expressed by various tissues and cell types. CK catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate...

, 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.

Eponym

WWS is named for Arthur Earl Walker

Arthur Earl Walker

Dr. A. Earl Walker, MD was an American neurosurgeon, neuroscientist and epileptologist remembered for the eponymous syndromes Dandy–Walker syndrome, Dandy–Walker-like syndrome and Walker–Warburg syndrome...

 and Mette Warburg. Its alternative names include Chemke’s syndrome and Pagon’s syndrome; named after Juan M. Chemke and Roberta A. Pagon.