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| DiseaseID |
HGD12 |
| Genetic
Disorder |
Cockayne syndrome
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| Gene
Name |
ERCC6 and ERCC8 gene |
| Description |
Edward Alfred Cockayne (1880–1956), after whom this disease is named, was a London physician who concentrated particularly on hereditary diseases of children. Cockayne syndrome is a rare inherited disorder in which people are sensitive to sunlight, have short stature, and have the appearance of premature aging. In the classical form of Cockayne syndrome (Type I), the symptoms are progressive and typically become apparent after the age of 1 year. An early onset or congenital form of Cockayne syndrome (Type II) is apparent at birth. Interestingly, unlike other DNA repair diseases, Cockayne syndrome is not linked to cancer.
After exposure to UV radiation (found in sunlight), people with Cockayne syndrome can no longer perform a certain type of DNA repair, known as "transcription-coupled repair." This type of DNA repair occurs "on the fly" right as the DNA that codes for proteins is being replicated. Two genes defective in Cockayne syndrome, CSA and CSB, have been identified so far. The CSA gene is found on chromosme 5. Both genes code for proteins that interacts with components of the transcriptional machinery and with DNA repair proteins.
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| Symptoms |
Because Cockayne syndrome affects many types of body cells, it affects many body systems. Some of its symptoms are:
• pinched, narrow face and beaked nose
• small head for body size (microcephaly)
• mental retardation
• sensitivity to sunlight
• short stature, hunched back (kyphosis)
• tremors, jerky movements, difficulty walking
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| Causes |
Mutations in the ERCC6 and ERCC8 genes cause Cockayne syndrome.
The ERCC6 and ERCC8 genes provide instructions for making proteins that are involved in repairing damaged DNA. If either gene is altered, DNA damage is not rapidly repaired. As a result, damaged DNA accumulates, which probably leads to impaired cell functions and eventually, cell death. Increased cell death likely contributes to features of Cockayne syndrome such as growth failure and premature aging. |
| Diagnosis |
CS may be diagnosed if both of the following major criteria and three of the five minor criteria are met:
MAJOR CRITERIA:
1. Height below fifth percentile for age and sex.
2. Developmental delay (absence or delayed occurrence of normal nervous system developmental milestones, such as ability to speak or walk).
MINOR CRITERIA:
1. Abnormal sensitivity to sunburning by UV-C from sunlight and
other sources.
2. Sensorineural (nerve) deafness.
3. Cataracts or pigmentary retinopathy (retinitis pigmentosum), either of which may cause blindness.
4. Unusually severe dental problems, including tooth decay.
5. Characteristic facies (facial apperance). This may include unusually large ears for head size ("Mickey Mouse ears"); small chin with prominent, pointed nose ("birdlike"); deficiency in adipose tissue ("fat") under skin, giving sunken eyes and skeletal appearance. Face overall may appear aged or wizened, and head size is likely to be unusually small for age and sex of patient (microcephaly).
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| Treatment |
There is no cure for Cockayne syndrome, so treatment focuses on relieving symptoms and improving the person's quality of life.
Physical and occupation therapy can help maintain joint function and reduce muscle contractures. Other specialists such as a neurologist and orthopedist provide important medical care. The person with Cockayne syndrome must also protect himself from sunlight with clothing and sunscreen, to reduce cell damage |
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