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.
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]).
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).