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Articles » Syndromes » Walker-Warburg syndrome

1999-05-09-12 Walker-Warburg syndrome © Silva

Walker-Warburg syndrome

Updated 2006-01-18 by Juliana Leite, MD

Original text 1999-05-09 Philippe Jeanty, MD, PhD & Sandra R Silva, MD

Synonyms: Lissencephaly type II, HARDE syndrome (hydrocephalus, agyria, retinal dysplasia, and encephalocele), muscle-eye-brain disease, cerebro-oculomuscular syndrome, cerebro-ocular dysplasia-muscular dystrophy, Warburg syndrome, Walker lissencephaly, encephalo-ophthalmic dysplasia, and oculocerebral malformation.

Definition: Walker-Warburg syndrome is a genetic disorder characterized by retinal detachment, cataract, micro-ophthalmia, and musculoskeletal and central nervous system anomalies (hydrocephalus, lissencephaly type II, cephalocele) associated with mental retardation. It was first reported by Walker in 1942 and reviewed by Warburg in 1971.

Incidence: Unknown.


Etiology: Autosomal-recessive inheritance.


DiagnosisDobyns reviewed 63 cases in 1989 and established the diagnostic criteria, which include lissencephaly type II, cerebellar malformations, retinal malformation (in general, retinal nonattachment), and congenital muscular dystrophy. Indeed, congenital muscular dystrophy is present in 100% of the cases. However, a wide variety of eye and cerebral manifestations have been reported, in addition to the main anomalies including: microphthalmia, buphthalmos, congenital glaucoma, cataract, optic nerve hypoplasia, persistent hyaloid artery, Dandy-Walker malformation, hydrocephalus, cephalocele, microcephaly, and agenesis of the corpus callosum. Based on this wide spectrum of defects, the association of any type of eye with cerebral malformations should raise the suspicion of Walker-Warburg syndrome. The finding of a concentric ring inside the vitreous body (the detached retina) or the presence of lipoma of the corpus callosum are very suggestive of the diagnosis. When prenatal sonographic findings are inconclusive, magnetic resonance imaging, computed tomography, electromyography, and autopsy studies are indicated after birth to provide accurate genetic counseling to the family.


Figure 1: Small cephalocele in a fetus with Walker-Warburg syndrome. The previous child of this family was similarly affected.

Genetic anomalies: Defect of 9q31.


Associated anomalies: Cleft lip and genital malformations may occasionally be found.


Differential diagnosisAnomalies associated with lissencephaly such as Miller-Dieker and Neu-Laxova are major differential diagnoses. Other disorders that should be excluded are Meckel syndrome, Fryns syndrome, trisomies 18 and 13, severe Fukuyama-type congenital muscular dystrophy (FCMD) (1) and maternal viral infections.


Recurrence Risk: The recurrence risk for couples with previously affected children is 25%.


Prognosis: Most of the newborns affected by Walker-Warburg syndrome die within the first year of life. Of those few who survive until 5 years of age, the majority have severe mental and developmental retardation.


Management: When detected before viability, termination of pregnancy can be offered. After viability, standard prenatal care is not altered.



[1] Walker AE. Lissencephaly. Arch. Neurol. Psychiatry, 1942, 48: 13-29

[2] Warburg M., The heterogeneity of microphthalmia in the mentally retarded. Birth Defects, 1971,VII (3): 136-152.

[3] Crowe C., Jassani M., Dickerman L. The prenatal diagnosis of the Walker-Walburg syndrome Prenat. Diaogn, 1986, 6: 177-185

[4] Dobyns WB., Pagon RA., Armstrong D., Curry CJR., Greenberg F., Grix A., Holmes LB., Laxova R., MichelsmVV., Robinow M., Zimmerman RL. Diagnostic criteria for Walker-Walburg syndrome. Am J Med Genet. 1989, 32: 195-210.

[5] Chemke J., Czernobilsky B., Mundel G., Barishak YR. A familial syndrome of central nervous system and ocular malformations. Clin. Genet., 1975, 7: 1-7

[6] Chitayat D., Toi A., Babul R., Levin A., Michaud J., Summers A., Rutka J., Blaser S., Becker L.E. Prenatal diagnosis of retinal nonattachment in the Walker-Walburg syndrome. Am J. Med. Genet., 1995, 56: 351-358 

[7] Jones KL. Walker-Warburg syndrome in Smith"s recognizable patterns of human malformation, W.B. Saunders Company - Philadelphia, Pennsylvania. 1997, 192-193 

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