Warburg syndrome: lethal neurodysplasia with autosomal recessive inheritance

Warburg syndrome is a recently recognized autosomal recessive neurodysplasia characterized by ventricular dilation, agyria, disorganized cortical cytoarchitecture, and dysgenesis of multiple other central nervous system structures. Because the disorder is lethal, with a 25% recurrence risk, it is crucial to distinguish Warburg syndrome from nonheritable phenocopies (caused by infectious agents and other teratogens) as well as from genetic disorders with a better prognosis. The clinical presentation of a markedly depressed newborn infant with hydrocephalus or ocular anomalies should suggest the diagnosis; computed tomography may be useful to demonstrate agyria as well as ventricular dilation. However, the distinctive neuropathologic finding of absent cerebral cortical lamination associated with numerous heterotopias appears to be diagnostic. Thus brain biopsy should be considered, especially at the time of ventricular shunting, whenever the clinical presentation suggests Warburg syndrome.