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

Cerebro-oculo-facio-skeletal syndrome

Cerebro-oculo-facio-skeletal (COFS) syndrome is a degenerative disorder that primarily involves the brain, eyes, and spinal cord.[1] Affected individuals have mild to severe intellectual disability, severely reduced muscle tone (hypotonia), impaired reflexes, vision impairment, and involuntary eye movements. Children with COFS syndrome have distinctive facial features, including low-set ears, small eyes, small head size (microcephaly), and a small jaw (micrognathia). They may also have abnormalities of the skull, limbs, heart, and kidneys.[2] Individuals with COFS syndrome are often diagnosed at birth. In many cases, the cause of the disorder is unknown. Some children with this condition have mutations in the ERCC1, ERCC2, ERCC5, or ERCC6 gene.[1] When an individual has the features of COFS syndrome and a mutation in the ERCC6 gene, they are said to have Cockayne syndrome type II. COFS syndrome is inherited in an autosomal recessive manner.[2] Most children with this condition do not live past age 5 years of age. Treatment involves supportive care and is based on an individual's symptoms.[1]
Last updated: 10/14/2016

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
Abnormal nasal morphology
Abnormal of nasal shape
Abnormal of shape of nose
[ more ] 		0005105
Aplasia/Hypoplasia of the cerebellum
Absent/small cerebellum
Absent/underdeveloped cerebellum
[ more ] 		0007360
Arthrogryposis multiplex congenita 0002804
Camptodactyly of finger
Permanent flexion of the finger
0100490
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Death in infancy
Infantile death
Lethal in infancy
[ more ] 		0001522
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip
[ more ] 		0000232
Feeding difficulties in infancy 0008872
Hypertonia 0001276
Joint stiffness
Stiff joint
Stiff joints
[ more ] 		0001387
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
Microphthalmia
Abnormally small eyeball
0000568
Muscular hypotonia
Low or weak muscle tone
0001252
Prominent metopic ridge 0005487
Severe global developmental delay 0011344
Short stature
Decreased body height
Small stature
[ more ] 		0004322
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
Abnormality of immune system physiology 0010978
Cutaneous photosensitivity
Photosensitive skin
Photosensitive skin rashes
Photosensitivity
Sensitivity to sunlight
Skin photosensitivity
Sun sensitivity
[ more ] 		0000992
Hypogonadism
Decreased activity of gonads
0000135
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation
[ more ] 		0001511
Reduced tendon reflexes 0001315
Seizure 0001250
Sensorineural hearing impairment 0000407
Short neck
Decreased length of neck
0000470
Visual impairment
Impaired vision
Loss of eyesight
Poor vision
[ more ] 		0000505
5%-29% of people have these symptoms
Abnormality of retinal pigmentation 0007703
Optic atrophy 0000648
Peripheral neuropathy 0009830
Talipes 0001883
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Last updated: 7/1/2020
Mutations in the ERCC1, ERCC2, ERCC5, and ERCC6 genes have been found to cause some cases of COFS syndrome. These genes provide instructions for making proteins that are involved in repairing damaged DNA.[3] If any of these genes are altered, DNA damage is not rapidly repaired. As a result, damaged DNA accumulates, which probably leads to impaired cell functions and eventually, cell death. It remains unclear how mutations in these genes lead to the signs and symptoms of COFS syndrome.

In many people, the cause of the disorder is unknown. Mutations in one or more as-yet unidentified genes may be responsible for the disorder in these cases.[1]
Last updated: 10/14/2016

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

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.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.
Treatment for COFS syndrome involves supportive care and is based on an individual's symptoms. People with this condition often require a feeding tube to obtain adequate nutrition.[1]
Last updated: 10/14/2016

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
Differential diagnoses include infectious fetopathies (cytomegalovirus, rubella, toxoplasmosis; see these terms) and MICRO syndrome (see this term) that can present as clinically similar to COFS syndrome, but with normal DNA repair.
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

  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

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.
  • The 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 Cerebro-oculo-facio-skeletal 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. Submit a new question

  • My granddaughter is 6-months-old and has microcephaly. The geneticist said there is a slight possibility she has COFS syndrome. Can you please give us more information? See answer


  1. NINDS Cerebro-Oculo-Facio-Skeletal Syndrome Information Page. National Institute of Neurological Disorders and Stroke Website. November 18, 2008; http://www.ninds.nih.gov/disorders/cofs/cofs.htm. Accessed 10/14/2016.
  2. Pr Hélène Dollful Pr Vincent Laugel. COFS syndrome. Orphanet. February 2009; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1466. Accessed 10/14/2016.
  3. Cassandra L. Kniffin. CEREBROOCULOFACIOSKELETAL SYNDROME 3; COFS3. OMIM. 9/23/2015; http://omim.org/entry/616570?search=ERCC5&highlight=ercc5. Accessed 10/14/2016.