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Handbook of Genetic Counseling/Zellweger Syndrome

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Zellweger Syndrome

Genetic Etiology

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  • 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

Incidence and Carrier Frequency

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  • Incidence is 1 in 40,000. Males and females are affected equally.

Clinical Features

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  • 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

Age of Onset, Natural History, Life Span

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  • 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.

Testing

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  • 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

Surveillance, Management, and Treatment Options

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  • Multidisciplinary early intervention
  • Oral administration of plasmalogens
  • Restricted phytanic acid intake
  • OT, PT, hearing aids, nutrition
  • Skeletal surveys (X-rays, CT and MRI)
  • Renal and abdominal ultrasounds

Differential Diagnoses

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  • Down syndrome is the most common

Notes

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The information in this outline was last updated in 2002.

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