Cockayne's Syndrome , also called Neill-Dingwall syndrome , is a rare and fatal autosomal recessive neurodegenerative disorder characterized by a failure of growth, developmental disorder from the nervous system, an abnormal sensitivity to sunlight (photosensitivity), eye disorders and premature aging. Failure to develop and neurological disorders are criteria for diagnosis, while photosensitivity, hearing loss, eye abnormalities, and cavities are another very common feature. Problems with any or all of the internal organs are possible. It is associated with a group of disorders called leukodystrophies, which is a condition characterized by the degradation of neurological white matter. The underlying disorder is a defect in the DNA repair mechanism. Unlike other DNA repair defects, patients with CS are not susceptible to cancer or infection. Cockayne's syndrome is a rare but damaging disease that usually causes death in the first or second decade of life. Specific gene mutations in Cockayne's syndrome are known, but the widespread effects and their association with DNA repair have not been well understood.
It was named after the English physician Edward Alfred Cockayne (1880-1956) who first described it in 1936 and described again in 1946. Neill-Dingwall's syndrome is named after Mary M. Dingwall and Catherine A. Neill. These women described the case of two brothers with Cockayne's syndrome and confirmed it was the same disease described by Cockayne. In their article, women contribute to the symptoms of the disease through the discovery of calcification in the brain. They also compared Cockayne's syndrome with what is now known as Hutchinson-Gilford progeria syndrome (HGPS), which is then called progeria, due to the advanced senescence that characterizes both disorders.
Video Cockayne syndrome
Genetika
Cockayne's syndrome is genetically classified as follows:
Mutation in the ERCC8 gene (also known as CSA) or the ERCC6 gene (also known as CSB) is the cause of Cockayne's syndrome. Mutations in the ERCC6 gene mutation make up ~ 70% of cases. Proteins made by these genes are involved in repairing damaged DNA through transcriptional fixing mechanisms, especially DNA in the active gene. DNA damage is caused by ultraviolet light from sunlight, radiation, or free radicals in the body. Normal cells can repair DNA damage easily before it is collected. If ERCC6 or ERCC8 gene is altered (as in Cockayne Syndrome), DNA damage is not corrected. When this damage accumulates, it can cause malformed cells or cell death. These cell deaths and malfunctions are likely to contribute to the symptoms of Cockayne syndrome such as premature aging and hypomyelination of neurons.
Maps Cockayne syndrome
DNA repair
In contrast to cells with normal improvement abilities, CSA and CSB deficiency cells are not particularly capable of repairing the cyclobutane-induced pyrimidine dimer induced by the action of ultraviolet (UV) light on activated transcription gene strands. This deficiency reflects a loss of ability to perform a DNA repair process known as transcription of nucleotide excision repair (TC-NER).
Inside damaged cells, CSA proteins usually localize DNA damage sites, especially cross-lines, double-strand breaks and multiple monoadducts. CSB proteins are also usually recruited to damaged DNA sites, and the fastest and most powerful recruitment is as follows: interstrand crosslinks & gt; double strand break & gt; monoadducts & gt; oxidative damage. CSB proteins form complexes with other DNA repair proteins, SNM1A (DCLRE1A), 5 '- 3' exonsuklease, which localize crosslinking between strings in a way that relies on transcription. The accumulation of CSB proteins in double-stranded DNA sites occurs in a way that relies on transcription and facilitates the restoration of homologous recombination from rest. During the G0/G1 phase of the cell cycle, DNA damage can trigger a CSB-dependent recombination repair process that uses RNA (not DNA).
The premature aging features of CS may be caused, at least in part, on deficiencies in DNA repair (see the DNA damage theory on aging).
Diagnosis
People with this syndrome have smaller head size than normal (microcephaly), short stature (dwarfism), their eyes are hollowed out, and they have an "old" look. They often have long legs with joint contractures (inability to relax the muscles in the joints), hunchbacks (kyphosis), and they may be very thin (cachetic), due to loss of subcutaneous fat. Their little chin, big ears, and pointy, thin noses often give an old appearance. Their skin with Cockayne syndrome is also frequently affected. Hyperpigmentation, varicose veins or spider veins (telangiectasia), and a serious sensitivity to sunlight are common, even in individuals without XP-CS. Often patients with Cockayne Syndrome will be very burned or blistered with very little exposure. The eyes of the patient can be affected by various ways and common eye disorders occur in CS. Cataract and corneal opacities (corneal opacity) are common. Loss and damage to the optic nerve, causing optic atrophy to occur. Nystagmus, or unconscious eye movements, and enlarged pupils show a loss of control of voluntary and unconscious muscle movement. Salt and retina pigmentation are also visible symptoms. Diagnosis is determined by special tests for DNA repair, which measures RNA recovery after exposure to UV radiation. Although associated with genes involved in nucleotide excision repair (NER), unlike xeroderma pigmentosum, CS is not associated with an increased risk of cancer.
Neurology
The imaging study reveals the lack of widespread myelin sheath from neurons in the white matter of the brain, and the general atrophy of the cortex. Calcification has also been found in the putamen, the area of ​​the forebrain that regulates movement and relief in some form of learning, along with in the cortex. In addition, the atrophy of the cerebellar central area found in patients with Cockayne syndrome can also lead to a lack of muscle control, especially the unconscious, and poor posture usually seen.
Type
- CS Type I, the "classic" form, is characterized by normal fetal growth with abnormalities occurring within the first two years of life. Vision and hearing decreases gradually. The central and peripheral nervous systems progressively deteriorate to death in the first or second decade of life as a result of serious neurological degradation. Cortical atrophy is less severe in Type I CS.
- Type II CS is present at birth (congenital) and much more severe than CS Type 1. It involves little neurologic development after birth. Death usually occurs at the age of seven years. This particular type has also been defined as cerebro-okuli-facio-skeletal syndrome (COFS) or Type II Shave-Type pen syndrome. COFS syndrome is so named because of its effect on the brain, the eyes, the face, and the skeletal system, as it often causes brain atrophy, cataracts, fat loss in the face, and osteoporosis. COFS syndrome can be subdivided into several conditions (COFS types 1, 2, 3 (associated with xeroderma pigmentosum) and 4). Usually patients with this early form of disorder exhibit more severe brain damage, including reduced white matter mielination, and wider calcifications, including in the cortex and basal ganglia.
- CS Type III, characterized by slow onset, is usually lighter than Type I and II. Often patients with Type III will live to adulthood.
- Xeroderma pigmentosum-Cockayne syndrome (XP-CS) occurs when a person also has xeroderma pigmentosum, another DNA repair disease. Some symptoms of each disease are expressed. For example, characteristic freckling abnormalities and XP pigments are present. Neurological disorders, flexibility, and backwardness of sex organs typical of CS are seen. However, the hypomyelination and facial features of a typical CS patient do not exist.
Treatment
There is no permanent cure for this syndrome, although patients can be treated according to their specific symptoms. The prognosis for those with Cockayne syndrome is poor, because death usually occurs at age 12. Treatment usually involves physical therapy and minor surgery to the affected organ, such as cataract removal. Also wearing sunscreen and protective clothing of the high-factor is recommended because patients with Cockayne syndrome are very sensitive to UV radiation. Optimal nutrition can also help. Genetic counseling for the elderly is recommended, since the disorder has a 25% chance of being forwarded to children in the future, and prenatal testing is also a possibility. Another important aspect is the prevention of CS recurrence in other siblings. Identification of the gene defects involved makes it possible to offer genetic counseling and antenatal diagnostic testing to parents who already have one child affected.
See also
- Accelerated aging disease
- Biogerontology
- degenerative disease
- Genetic disorders
- CAMFAK syndrome - is considered a form (or part) of Cockayne syndrome
References
External links
- 'Amy and Friends' - UK-based charity supports children with Cockayne Syndrome
- Shared and Maintained a Cockayne Syndrome Network
- cockayne in NIH/UW GeneTests
- This article incorporates some public domain text from the U.S. National Medical Library.
Source of the article : Wikipedia
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