Cerebro Oculo Facio Skeletal Syndrome

Cerebro Oculo Facio Skeletal Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Cerebro Oculo Facio Skeletal Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Cerebrooculofacioskeletal Syndrome
  • COFS Syndrome
  • Pena Shokeir II Syndrome
  • Pena Shokeir Syndrome Type II
  • Cockayne Syndrome type II

Disorder Subdivisions

  • None

General Discussion

Cerebro-oculo-facio-skeletal (COFS) syndrome is a genetic degenerative disorder of the brain and spinal cord that begins before birth. The disorder is characterized by growth failure at birth and little or no neurological development, structural abnormalities of the eye and fixed bending of the spine and joints. Abnormalities of the skull, face, limbs and other parts of the body may also occur. COFS syndrome is inherited as an autosomal recessive genetic trait. COFS is now considered to be part of the spectrum of disorders within Cockayne syndrome.

Symptoms

Cerebro-oculo-facio-skeletal syndrome was first described in 1974. Symptoms of this disorder include unusual craniofacial features. These may include an extremely small head (microcephaly), an unusually prominent nose, abnormally small eyes, clouding of the eye's lens (cataract), and a horizontally narrow opening between the eyelids (blepharophimosis). The ears are abnormally large, the upper lip overlaps the lower, the groove in the upper lip (philtrum) is abnormally long, and the jaw is unusually small (micrognathia).



In most patients, fixed bending of the elbows and knees (flexion contractures), a hunched back (kyphosis), and bending of one or more fingers (camptodactyly) occurs. Infants with cerebro-oculo-facio-skeletal syndrome usually have so-called "rocker bottom" feet and a groove over the length of the soles of the feet. A deformity of the hip (coxa valga) and porous bones (osteoporosis) may also occur.



Other features of this disorder include wide-set nipples, failure to thrive, slowed growth (developmental retardation), lack of muscle tone (hypotonia), feeding difficulties and one line in the palm of the hand formed by fusion of the usual two lines (simian crease). Children with cerebro-oculo-facio-skeletal syndrome have an increased vulnerability to respiratory infections.



Individuals with COFS syndrome show progressive deterioration and rarely survive beyond seven years.

Causes

Cerebro-oculo-facio-skeletal syndrome is an autosomal recessive genetic disorder. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.



All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.



COFS syndrome has been found to be associated with mutations in genes responsible for repairing DNA damage. These genes are called excision repair cross-complementing genes and include ERCC6, ERCC8 and ERCC2.

Affected Populations

Cerebro-oculo-facio-skeletal syndrome is a very rare disorder present at birth. It affects males and females and occurs in many ethnic groups.

Standard Therapies

Diagnosis

The diagnosis of COFS syndrome is often made based on physical features seen at birth. X-ray studies may reveal displacement of the small foot bones between the ankle and toes (second metatarsals) and neuroimaging studies may show reduced white matter with gray matter mottling. DNA repair studies on skin fibroblast cells may help to confirm a diagnosis of COFS syndrome. Molecular genetic testing to identify mutations in the excision repair genes is available on a research basis only.



Treatment

Treatment of COFS syndrome is symptomatic and supportive. Genetic counseling is recommended for families of children with the disorder.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Rosser T and Pearl PL. Cerebro-Oculo-Facio-Skeletal Syndrome. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003: 520-521.



Jones KL. Smith's recognizable patterns of human malformation, 4th ed. Philadelphia: WB Saunders, 1998.



JOURNAL ARTICLES

Graham JM, Anyan-Yeboa K, Raams A, et al. Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair defect and a mutated XPD gene, with prenatal diagnosis in a triplet pregnancy. Am J Hum Genet 2001;69:291-300.



Meira LB, Graham JM, Greenberg CR, et al. Manitoba aboriginal kindred with original cerebro-oculo-facio-skeletal syndrome has a mutation in the Cockayne syndrome group B (CSB) gene. Am J Hum Genet 2000;66:1221-8.



Graham JR, Greenberg CR, Anyane-Yeboa K, et al. COFS syndrome caused by defective nucleotide excision repair . Am J Hum Genet 1998;63:A33.



Del Bigio MR, Greenberg CR, Rorke LB, et al. Neuropathologic findings in eight patients with cerebro-oculo-facio-skeletal (COFS) syndrome. J Neuropathol 1997;56:1147-1157.



Harden CL, Tuchman AJ, Daras M. Infantile spasms in COFS syndrome. Pediatr Neurol 1991;7:302-304.



Hwang WS, Trevenen CL, Greenberg C, et al. Chondro-osseus changes in cerebro-oculo-facial-skeletal syndrome. J Pathol 1982;138:33-40.



FROM THE INTERNET

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University Press; Entry No. 214150; Last Update: 9/20/01.



Nance MA , (updated 15 October 2001). Cockayne Syndrome In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2003. Available at http://www.genetests.org Accessed 8/03.

Resources

Children's Craniofacial Association

13140 Coit Road

Suite 517

Dallas, TX 75240

USA

Tel: (214)570-9099

Fax: (214)570-8811

Tel: (800)535-3643

Email: contactCCA@ccakids.com

Internet: http://www.ccakids.com



March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



FACES: The National Craniofacial Association

PO Box 11082

Chattanooga, TN 37401

Tel: (423)266-1632

Fax: (423)267-3124

Tel: (800)332-2373

Email: faces@faces-cranio.org

Internet: http://www.faces-cranio.org



AmeriFace

P.O. Box 751112

Limekiln, PA 19535

USA

Tel: (702)769-9264

Fax: (702)341-5351

Tel: (888)486-1209

Email: info@ameriface.org

Internet: http://www.ameriface.org



NIH/National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

Tel: (301)496-5751

Fax: (301)402-2186

Tel: (800)352-9424

TDD: (301)468-5981

Internet: http://www.ninds.nih.gov/



National Foundation for Facial Reconstruction

333 East 30th Street, Lobby Unit

New York, NY 10016

Tel: (212)263-6656

Fax: (212)263-7534

Internet: http://www.nffr.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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