National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Zellweger syndrome


Other Names:
Cerebrohepatorenal syndrome; CHR; ZWS; Cerebrohepatorenal syndrome; CHR; ZWS; ZS; Zellweger leukodystrophy See More
Categories:
Zellweger syndrome is the most severe form of a spectrum of conditions called Zellweger spectrum. The signs and symptoms of Zellweger syndrome typically appear during the newborn period and may include poor muscle tone (hypotonia), poor feeding, seizures, hearing loss, vision loss, distinctive facial features, and skeletal abnormalities.[1][2] Affected children also develop life-threatening problems in other organs and tissues, such as the liver, heart, and kidneys.[2] Children with Zellweger syndrome usually do not survive beyond the first year of life. Zellweger syndrome is caused by mutations in any one of at least 12 genes; mutations in the PEX1 gene are the most common cause. It is inherited in an autosomal recessive manner.[1] There is no cure for Zellweger syndrome; treatment is generally symptomatic and supportive.
Last updated: 12/7/2014
The signs and symptoms of Zellweger syndrome typically become apparent within the first few hours or days of life. Affected newborns often have poor muscle tone (hypotonia); seizures; feeding difficulties; liver cysts with liver dysfunction; vision loss; hearing loss; and distinctive facial characteristics including a flattened face, broad nasal bridge, high forehead, upslanting palpebral fissures, and epicanthal folds.[1][2][3] Some people also have an abnormally small or large head size (microcephaly or macrocephaly, respectively); protruding tongue; neck skin folds; cataracts; glaucoma; and/or nystagmus.[4] Many affected infants have skeletal abnormalities, which may include a large space between the bones of the skull and bone spots known as chondrodysplasia punctata that can be seen with an X-ray.[2] The function of the central nervous system (brain and spinal cord) is typically severely affected.[3] Children with Zellweger syndrome also develop life-threatening problems in other organs and tissues, such as the liver, heart, and kidneys.[2]
Last updated: 12/7/2014

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment
[ more ] 		0100543
Corneal opacity 0007957
Death in infancy
Infantile death
Lethal in infancy
[ more ] 		0001522
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root
[ more ] 		0005280
EEG abnormality 0002353
Epicanthus
Eye folds
Prominent eye folds
[ more ] 		0000286
Epiphyseal stippling
Speckled calcifications in end part of bone
0010655
External ear malformation 0008572
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Feeding difficulties in infancy 0008872
Flat face
Flat facial shape
0012368
Hepatic failure
Liver failure
0001399
Hepatomegaly
Enlarged liver
0002240
High forehead 0000348
Jaundice
Yellow skin
Yellowing of the skin
[ more ] 		0000952
Profound global developmental delay 0012736
Reduced tendon reflexes 0001315
Respiratory insufficiency
Respiratory impairment
0002093
Severe muscular hypotonia
Severely decreased muscle tone
0006829
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Skeletal dysplasia 0002652
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582
Very long chain fatty acid accumulation 0008167
Wide anterior fontanel
Wider-than-typical soft spot of skull
0000260
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ] 		0000431
30%-79% of people have these symptoms
Abnormal chorioretinal morphology 0000532
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Clitoral hypertrophy
Enlarged clitoris
0008665
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Flat occiput 0005469
High palate
Elevated palate
Increased palatal height
[ more ] 		0000218
Hydronephrosis 0000126
Hypospadias 0000047
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ] 		0000256
Malabsorption
Intestinal malabsorption
0002024
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Multicystic kidney dysplasia 0000003
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Optic atrophy 0000648
Polymicrogyria
More grooves in brain
0002126
Posterior embryotoxon 0000627
Premature birth
Premature delivery of affected infants
Preterm delivery
[ more ] 		0001622
Pyloric stenosis 0002021
Seizure 0001250
Sensorineural hearing impairment 0000407
Underdeveloped supraorbital ridges
Flattened bony protrusion above eyes
0009891
Visual impairment
Impaired vision
Loss of eyesight
Poor vision
[ more ] 		0000505
5%-29% of people have these symptoms
Abnormality of coagulation 0001928
Abnormality of the tongue
Abnormal tongue
Tongue abnormality
[ more ] 		0000157
Brushfield spots 0001088
Glaucoma 0000501
Primary adrenal insufficiency 0008207
Thickened nuchal skin fold
Thickened skin folds of neck
Thickened skin over the neck
[ more ] 		0000474
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Percent of people who have these symptoms is not available through HPO
Abnormal electroretinogram 0000512
Abnormality of the helix 0011039
Adrenal hypoplasia
Small adrenal glands
0000835
Albuminuria 0012592
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine
[ more ] 		0003355
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils
[ more ] 		0000463
Aplasia/Hypoplasia of the corpus callosum 0007370
Areflexia
Absent tendon reflexes
0001284
Autosomal recessive inheritance 0000007
Bell-shaped thorax 0001591
Brachyturricephaly
High, prominent forehead
0000244
Breech presentation
Feet or buttocks of fetus positioned near opening of uterus
0001623
Cubitus valgus
Outward turned elbows
0002967
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development
[ more ] 		0002750
Elevated circulating long chain fatty acid concentration 0003455
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Gray matter heterotopia 0002282
High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth
[ more ] 		0002705
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Hypoplastic olfactory lobes 0006894
Hyporeflexia
Decreased reflex response
Decreased reflexes
[ more ] 		0001265
Intellectual disability, progressive
Mental retardation, progressive
Progressive mental retardation
[ more ] 		0006887
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation
[ more ] 		0010864
Intrahepatic biliary dysgenesis 0001401
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue
[ more ] 		0000158
Malar flattening
Zygomatic flattening
0000272
Metatarsus adductus
Front half of foot turns inward
0001840
Muscular hypotonia
Low or weak muscle tone
0001252
Opacification of the corneal stroma 0007759
Optic disc pallor 0000543
Patent ductus arteriosus 0001643
Pigmentary retinopathy 0000580
Posteriorly rotated ears
Ears rotated toward back of head
0000358
Prolonged neonatal jaundice
Prolonged yellowing of skin in newborn
0006579
Protruding tongue
Prominent tongue
Tongue sticking out of mouth
[ more ] 		0010808
Pulmonary hypoplasia
Small lung
Underdeveloped lung
[ more ] 		0002089
Renal cortical microcysts 0004734
Rocker bottom foot
Rocker bottom feet
Rocker-bottom feet
Rockerbottom feet
[ more ] 		0001838
Round face
Circular face
Round facial appearance
Round facial shape
[ more ] 		0000311
Single transverse palmar crease 0000954
Subependymal cysts 0002416
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot
[ more ] 		0001762
Ulnar deviation of the hand 0009487
Ulnar deviation of the hand or of fingers of the hand 0001193
Widely patent fontanelles and sutures 0004492
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Last updated: 7/1/2020
Zellweger syndrome is an autosomal recessive condition caused by changes (mutations) in any one of at least 12 different genes that are involved in the creation and proper function of peroxisomes. Peroxisomes are structures in cells that are involved in many chemical processes needed for the body to function properly. They are vital for the proper breakdown of fatty acids and the production of certain lipids (fats) that are important to the nervous system and digestion. They are also play a role in waste disposal and help with the development and function of the brain. Mutations in the genes responsible for Zellweger syndrome cause dysfunction of peroxisomes, which leads to the signs and symptoms of the condition.[5]

Almost 70% of individuals with a Zellweger spectrum disorder have a mutation in the PEX1 gene.[5] The other genes associated with the Zellweger spectrum each account for a smaller percentage of cases.[2] To see a list of the genes associated with Zellweger syndrome click here.
Last updated: 12/7/2014
Zellweger syndrome is inherited in an autosomal recessive manner.[1] This means that a person must have a change (mutation) in both copies of the responsible gene in order to have the condition. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers do not have signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.
Last updated: 12/7/2014
A diagnosis of a Zellweger syndrome is usually suspected when characteristic signs and symptoms are present at birth, including the distinctive facial features. Tests that measure or detect specific substances in blood or urine samples can confirm a diagnosis of Zellweger syndrome. For example, detection of elevated levels of very long chain fatty acids (VLCFA) in the blood is the most commonly used screening test. Additional tests on blood and urine samples to find other substances associated with the condition may be performed. An ultrasound may be used to look for cysts on the kidneys or an enlarged liver. A genetic test to find a mutation in one of the genes associated with Zellweger spectrum disorders may also be used to confirm the diagnosis.[5][1]
Last updated: 12/7/2014

Yes. Clinical genetic testing is available for the twelve genes known to cause Zellweger syndrome.[1] Carrier testing for at-risk relatives and prenatal testing are possible if the two disease-causing mutations in the family are known.

The Genetic Testing Registry (GTR) is a centralized online resource for information about genetic tests. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Last updated: 12/7/2014

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
There is currently no cure or effective treatment for Zellweger syndrome. Management is supportive and based on the signs and symptoms present in each person. For example, infants with feeding issues may require placement of a feeding tube to ensure proper intake of calories. Care is usually handled by a team of specialists that may include pediatricians, neurologists, surgeons, audiologists (treat hearing problems), ophthalmologists (treat vision problems), and orthopedists (treat skeletal abnormalities).[5][1][6]
Last updated: 12/7/2014
The long-term outlook (prognosis) for infants with Zellweger syndrome is very poor. Most infants do not survive past the first 6 months of life, and usually succumb to respiratory distress, gastrointestinal bleeding, or liver failure.[6] Although no specific treatment for Zellweger syndrome currently exists, significant progress has been made in understanding the molecular and biochemical aspects of the condition, which researchers believe will lead to new research strategies and new therapies in the future.[5]
Last updated: 12/7/2014

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The main differential diagnoses include Usher syndrome I and II, other PBD disorders (see these terms), single enzyme defects in peroxisome fatty acid beta-oxidation, and disorders that feature severe hypotonia, neonatal seizures, liver dysfunction or leukodystrophy.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Zellweger syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Organizations Providing General Support

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Zellweger syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Steven J Steinberg, PhD, Gerald V Raymond, MD, Nancy E Braverman, MS, MD, and Ann B Moser, BA. Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum. GeneReviews. May 2012; http://www.ncbi.nlm.nih.gov/books/NBK1448/.
  2. Zellweger spectrum. Genetics Home Reference. June 2015; http://ghr.nlm.nih.gov/condition/zellweger-spectrum.
  3. Zellweger syndrome. Orphanet. December 2012; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=912.
  4. Zellweger syndrome. Orphanet. January 2008; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=912. Accessed 12/29/2011.
  5. Zellweger Spectrum Disorders. NORD. September 15, 2008; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/363/viewAbstract.
  6. NINDS Zellweger Syndrome Information Page. National Institute of Neurological Disorders and Stroke. October 2012; http://www.ninds.nih.gov/disorders/zellweger/zellweger.htm.