The diagnosis of Zellweger syndrome is established by fibroblast culture and liver biopsy. They do not show peroxisomes when stained for peroxisomal enzymes. Electromicroscopy of the same tissue shows that the peroxisomal membranes are present. They are called “ghost peroxisomes” because the membrane is present but the enzymes are not. Genetic defects at 7q11.23 and 1p22-p21 are associated with Zellweger syndrome. Most patients with Zellweger syndrome die during the first year of life. Survivors are mentally retarded. Zellweger syndrome has an autosomal recessive inheritance.

Walker-Warburg Syndrome
The acronym HARD +/- E has being used for this disorder. This acronym stands for the first letter of the major features of this condition: hydrocephalus, agyria (cerebral and cerebellar), retinal dysplasia, and occasionally encephalocele. In addition to retinal dysplasia, other ocular abnormalities include microphthalmia (Figure 161.1 [A]), vitreous abnormalities, retinal detachment, glaucoma, cataracts, and corneal opacities. Neonates with Walker-Warburg syndrome are hypotonic and usually have seizures. Arthrogryposis is usually distal. The brain abnormalities in Walker-Warburg syndrome are probably due to a defect in the external basal lamina of the brain. The external basal lamina of the brain is the boundary that stops the neuronal migrational process. Failure of the external basal lamina to develop causes the neurons to cross over sulci and into the meninges creating a flat brain and engulfing the meninges. Walker-Warburg syndrome is familial. The familial incidence is most likely due to an autosomal recessive inheritance, but the possibility of a persistent intrauterine viral infection affecting several members in one family has been considered. Walker-Warburg syndrome is diagnosed by MRI. The MRI shows smooth cerebral and cerebellar surfaces, large lateral ventricles in relation to cerebral mass, and absence of cerebellar vermis (Figure 161.1 [B,C]).

A	B	C

Figure 161.1.—Walker-Warburg syndrome. [A] T2-axial weighted image demonstrates microphthalmia; [B] T1-axial weighted image demonstrates lissencephaly with large lateral ventricles; and [C] T1-axial weighted image demonstrates agenesis of the cerebellar vermis (cerebellar hemispheres in apposition without an intervening vermis).