Handbook of Genetic Counseling/Zellweger Syndrome

Zellweger Syndrome

Genetic Etiology

Mode of inheritance: Autosomal recessive with non-allelic heterogeneity.
Chromosome location: 2p15, 1q22, 12p13.3, 7q21-q22, 6q23-q24
Molecular genetics: Phenotype caused by mutation in any of several genes involved: in peroxisome biogenesis (peroxi-1, -2, -3, -5, -6, or -12).
Peroxisomes are subcellular organelles that play a role in lipid metabolism--these are absent

Craniofacial Features
- Flat occiput and face
- Anteverted nares
- Epicanthal folds
- Brushfield spots
- High forehead
- Large fontanels
- Shallow orbits
Ocular Features
- Cataracts
- Hypoplastic optic disk
Auditory Features
- Abnormal helices
- Deafness
Neurological Features
- Early developmental delay
- Seizures
- Brain migrational abnormalities
- MR in survivors
- Brain malformations including microgyria, heteropias, subependymal cysts, astrocytosis and gliosis, hypoplastic corpus callosum, hypoplastic olfactory lobes
Extremities
- Single palmar creases
- Joint contractures
- Stippled epiphyses
- Camptodactyly
Cardiovascular Features
- Cardiac septal defects
- PDA
Other Features
- Hepatomegaly
- Postnatal growth deficiency and low birth weight
- Poor suck
- Albuminuria and cysts of glomeruli in kidneys
- Elevated serum iron level and evidence of excess iron storage
- Absent liver peroxisomes

Most babies are born breech and exhibit failure to thrive. Some developed icterus and bloody stool.
Vast majority of children die within the first year of life. Those who survive have profound mental retardation. Average life span is 12-13 weeks.

Diagnosis is made through DNA testing.
Increase in plasma and fibroblasts of very-long-chain fatty acids and lack of dihydroxyacetone phosphate acyltransferase (DHAP-AT) are biochemical markers for this syndrome

The information in this outline was last updated in 2002.