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 Incidence and Carrier Frequency Incidence is 1 in 40,000. Males and females are affected equally. Clinical Features 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 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 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 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 Down syndrome is the most common Notes The information in this outline was last updated in 2002.