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