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Disease Profile

Cerebro-oculo-facio-skeletal syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

COFS syndrome; Pena-Shokeir syndrome type 2

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Eye diseases;

Summary

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]

Symptoms

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.

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

Cause

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]

Diagnosis

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

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]

Learn more

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.

References

  1. NINDS Cerebro-Oculo-Facio-Skeletal Syndrome Information Page. National Institute of Neurological Disorders and Stroke Website. November 18, 2008; https://www.ninds.nih.gov/disorders/cofs/cofs.htm. Accessed 10/14/2016.
  2. Pr Hélène Dollful Pr Vincent Laugel. COFS syndrome. Orphanet. February 2009; https://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; https://omim.org/entry/616570?search=ERCC5&highlight=ercc5. Accessed 10/14/2016.

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