Cockayne Syndrome

Cockayne Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Cockayne 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

  • CS
  • Deafness-Dwarfism-Retinal Atrophy
  • Dwarfism with Renal Atrophy and Deafness
  • Neill-Dingwall Syndrome
  • Progeroid Nanism

Disorder Subdivisions

  • Classical Form, Cockayne Syndrome Type I (Type A)
  • Congenital Form, Cockayne Syndrome Type II (Type B)
  • Late Onset, Cockayne Syndrome Type III (Type C)

General Discussion

Cockayne Syndrome (CS) is a rare form of dwarfism. It is an inherited disorder whose diagnosis depends on the presence of three signs (1) growth retardation, i.e. short stature, (2) abnormal sensitivity to light (photosensitivity), and (3) prematurely aged appearance (progeria). In the classical form of Cockayne Syndrome (CS type I) the symptoms are progressive and typically become apparent after the age of one year. An early onset or congenital form of Cockayne Syndrome (CS type II) is apparent at birth (congenital). There is a third form, known as Cockayne Syndrome Type III (CS type III), that presents later in the child's development and is generally a milder form of the disease. A fourth form; now recognized as Xeroderma pigmentosa-Cockayne syndrome (XP-CS), combines features of both of these disorders.

Symptoms

The symptoms of all forms of Cockayne Syndrome are similar. The different types of the disease are defined by the age of the onset.



CS type I, the classical form, is characterized by a normal appearing newborn whose symptoms may not become apparent until after the first year. Height and weight, as well as other indicators of size and growth are much within the 5th percentile. Vision, hearing, and nervous system functioning (central and peripheral) gets worse over time and seriously severe disability may result.



The few cases of congenital CS type II that have been reported are characterized by obvious growth failure at birth along with little or no neurological development after birth. Serious vision impairments (cataracts and other structural abnormalities of the eye) are usually present at birth. Early skeletal aberrations occur as well. It is likely that CS type II includes some patients previously diagnosed with cerebro-oculo-facial syndrome (COFS) and Pena-Shokeir type II syndrome due to the identification of a common gene defect in these patients.



CS type III is rarer still and is characterized by essentially normal growth and mental development during the early years but interrupted by the late onset of the typical symptoms of CS.



XP-CS is the most rare form and includes the features of both diseases. Widespread freckling and early skin cancers are typical of xeroderma pigmentosa and short stature, mental retardation and sexual underdevelopment are consistent with CS.



The major characteristics of Cockayne Syndrome include the stunting of normal growth (dwarfism) during late infancy, extreme sensitivity to light (photosensitivity), and a prematurely aged appearance (progeroid). The skin appears wrinkled and aged, especially on the face, arms, and legs, due to the loss of fat under the skin (subcutaneous adipose tissue). Children with this disorder may scar easily and have an increased amount of color (pigmentation) in the skin.



Children with Cockayne Syndrome have unusual physical features including an abnormally small head (microcephaly), an unusually thin nose, a "hollow" or sunken appearance to the eyes, large misshapen ears, poor eyelid closure, and/or the abnormal forward projection of both the upper and lower jaws (prognathism). There may be an unusual amount of dental decay due to the abnormal placement of the teeth. Affected individuals typically have large hands and feet, and unusually long arms and legs in proportion to the size of their body. Joints may also be abnormally large and remain in a fixed position (flexed), and the spine may be curved outward when viewed from the side (kyphosis). Other features of Cockayne Syndrome may include a decrease in the amount of sweating (hypohidrosis), lack of proper tearing in the eyes, and/or the premature graying of the hair.



Other symptoms of Cockayne Syndrome may include an abnormal blue tint to the skin (cyanosis) on the arms and legs, which may also feel cold to the touch. Neurological symptoms may include rhythmic, quivering movements (tremors), an unsteady gait (ataxia), and/or the inability to coordinate movement. Affected children may experience varying degrees of mental retardation, partial loss of hearing, and/or the progressive loss of previously acquired intellectual abilities.



The symptoms of Cockayne Syndrome that affect the eyes (ocular) may include progressive clouding of the lens of the eyes (cataracts), loss of vision because of the wasting of the nerve fibers within the eyes (optic atrophy), degeneration of the retina, and/or the abnormal accumulation of retinal coloration (pigmentation).



Some people with Cockayne Syndrome may also have abnormally high blood pressure (hypertension), an enlarged liver (hepatomegaly), and/or the premature accumulation of fatty plaques on the walls of the arteries around the heart (arteriosclerotic disease). Adults with this disorder may be sexually underdeveloped.

Causes

At the molecular level, CS is caused by a defect in one of the genes involved in the normal repair of DNA that has been damaged by ultraviolet light. This is the body's natural defense against sunburn. Exposure to the ultraviolet component of sunlight damages DNA but the cell is no longer able to repair the damaged DNA as it is produced and it accumulates in the cell.



It is likely, or at least suspected, that some of the genes which cause CS are also involved in protein synthesis, and that the other signs of CS are the result of the production and accumulation of abnormal proteins in the cell.



The gene responsible for CS-type I has been mapped to chromosome 5 and is called ERCC8. The gene for CS-type II has been mapped to chromosomal locus 10q11 and is called ERCC6. Mutations in ERCC6 account for about 75% of cases, while mutations in ERCC8 cause about 25% of cases.



Cockayne Syndrome is inherited as an autosomal recessive genetic trait. Human traits, including the classic genetic diseases, are determined by two genes, one received from the father and one from the mother. Recessive 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 will usually 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.

Affected Populations

Cockayne Syndrome is very rare and affects males and females in equal numbers. There are no indications of ethnic or racial partiality. The incidence of CS is less than 1 case per 250,000 live births in the U.S. As of 1992, about 140 cases of CS had been reported in the literature.

Standard Therapies

The treatment of Cockayne Syndrome is symptomatic and supportive. Specialized imaging testing (MRI) may demonstrate the loss of the fatty covering (demyelination) on some nerve fibers in the brain.



A supportive team approach may be of benefit for children with Cockayne Syndrome and may include special education, physical therapy, and other medical, social, and/or vocational services. Genetic counseling may benefit family members.

Investigational Therapies

The National Caner Institute is recruiting patients for a study designed to examine the clinical and laboratory abnormalities in patients with defective DNA repair: Xeroderma pigmentosum (XP), Cockayne syndrome (CS), XP-CS, or Trichothiodystrophy. Only patients with XP have an increases susceptibility to cancer. Through this study, researchers hope to better understand the mechanism of cancer prevention by DNA repair.



For further information contact:



Patient Recruitment and Liaison Office

National Cancer Institute (NCI)

9000 Rockville Pike

Bethesda, MD 20892



Tel: 800-411-1222

e-mail prpl@mail.cc.nih.gov



Study Identification Number are: 990099;99-c-0099



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

Cleaver JE, Kraemer KH. Xeroderma Pigmentosum and Cockayne Syndrome. In: Scriver CR, et al., eds. The Molecular Basis of Inherited Disease. 7th Ed. New York, NY; McGraw-Hill Companies, Inc; 1995:4393-4419.



Gorlin RJ, et al., eds. Syndromes of the Head and Neck, 3rd ed. New York, NY: Oxford University Press; 1990:492-94.



REVIEW ARTICLES

Cleaver JE, Crowley E. UV damage, DNA repair and skin carcinogenesis. Front Biosci. 2002;7:d1024-43.



Svejstrup JQ. Mechanisms of transcription-coupled DNA repair. Nat Rev Mol Cell Biol 2002;58:2085-97.



Lindenbaum Y, Dickson D, Rosenbaum P, et al. Xeroderma pigmentosum/Cockayne syndrome complex: first neuropathological study and review of eight other cases. Eur J Paediatr Neurol. 2001;5:225-42.



Tuteja N, Tuteja R. Unraveling DNA repair in human: molecular mechanisms and consequences of repair defect. Crit Rev Biol. 2001;36:261-90.



Van Brabant AJ, Stan R, Ellis NA. DNA helicases, genomic instability, and human genetic diseases. Annu Rev Genomics Hum Genet. 2000;1:409-59.



Rapin I, Lindenbaum Y, Dickson DW, et al. Cockayne syndrome and xeroderma pigmentosum. Neurology. 2000;55:1442-49.



Martin GM, Oshima J. Lessons from human progeroid syndromes. Nature;2002;408:263-66.



FROM THE INTERNET

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University;

Entry No: 216400; Last Update 8/8/02

Entry No: 133510; Last Update 7/31/02

Entry No: 216411; Last Update 3/5/02



Nance MA. Cockayne Syndrome. GENEREVIEWS. Last Revision: 15 October 2001 12pp.



Carter SM, Gross SJ. Cockayne Syndrome. eMedicine Journal. 2002;3:7pp.



Blanchet-Bardon C. Cockayne Syndrome. Orphanet. 1p.



CONSUMER RESOURCES

Share and Care. What is Cockayne Syndrome.

www.cockayne-syndrome.org/English/US_What_is CS.htm



Share and Care. (Busch DB.) Cockayne's Syndrome Handbook 1998:5pp.

http://members.aol.com/DBBusch/shareandcare.cshandbook.htm



Share and Care News 2001:6pp.

www.cockayne-syndrome.org/English/US/_Newsletter.htm



NCBI. Genes and diseases, CSA on chromosome 5.

www.nlm.nih.gov/disease/Cockayne.html

Resources

CLIMB (Children Living with Inherited Metabolic Diseases)

Climb Building

176 Nantwich Road

Crewe, CW2 6BG

United Kingdom

Tel: 4408452412173

Fax: 4408452412174

Email: enquiries@climb.org.uk

Internet: http://www.CLIMB.org.uk



Human Growth Foundation

997 Glen Cove Avenue

Suite 5

Glen Head, NY 11545

Tel: (516)671-4041

Fax: (516)671-4055

Tel: (800)451-6434

Email: hgf1@hgfound.org

Internet: http://www.hgfound.org/



MAGIC Foundation

6645 W. North Avenue

Oak Park, IL 60302

Tel: (708)383-0808

Fax: (708)383-0899

Tel: (800)362-4423

Email: mary@magicfoundation.org

Internet: http://www.magicfoundation.org



Share and Care Cockayne Syndrome Network, Inc.

P.O. Box 282

Waterford, VA 20197

USA

Tel: (703)727-0404

Email: cockaynesyndrome@gmail.com

Internet: http://www.cockayne-syndrome.org



Progeria Research Foundation, Inc.

2 Bourbon Street

Suite 208

Peabody, MA 01960

USA

Tel: (978)535-2594

Fax: (978)535-5849

Email: info@progeriaresearch.org

Internet: http://www.progeriaresearch.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/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



Let Them Hear Foundation

1900 University Avenue, Suite 101

East Palo Alto, CA 94303

Tel: (650)462-3174

Fax: (650)462-3144

Email: info@letthemhear.org

Internet: http://www.letthemhear.org



Perkins School for the Blind

175 North Beacon Street

Watertown, MA 02472

Tel: (617)924-3434

Fax: (617)926-2027

Email: Info@Perkins.org

Internet: http://www.Perkins.org



National Consortium on Deaf-Blindness

The Teaching Research Institute

345 N. Monmouth Avenue

Monmouth, OR 97361

Tel: (800)438-9376

Fax: (503)838-8150

Tel: (800)438-9376

TDD: (800)854-7013

Email: info@nationaldb.org

Internet: http://www.nationaldb.org



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.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.