Various types of leukemia develop at an average age of twenty-two. Patients who survive beyond the age of twenty-two develop solid tumors at an average age
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of thirty-five. These tumors are fortunately sensitive to chemotherapy and radiotherapy. With an increase in age, resistance to infections gradually improves and so does the skins’ photosensitivity.
Cause of the Disease
The syndrome is caused by mutation in the gene designated BLM which has been traced to chromosome 15q26.1. The protein encoded by the normal gene has DNA ligase activity and functions in the maintaining genomic stability. The DNA ligase activity is assumed in some way to manipulate DNA. Increased sister chromatid exchanges and chromosomal instability also occur, which is assumed to be responsible for the phenotype and the cancer predispostion. BLM is absent from cells in most persons with Bloom’s Syndrome, which leads to the conclusion that that its normal activity affects directly or indirectly the maintenance of genomic stability. In order to maintain leads into BLM’s exact function or functions, its distribution has been examined in cell culture. In interphase cells, BLM is only located in the nucleus. In early post- telophase cells it is barely visible. It then increases in amount, being both diffuse and also concentrating in multiple, very small, brightly fluorescing centers. In addition to discrete foci, larger but less intensively fluorescing, irregularly shaped aggregates of BLM form in many nuclei. At metaphase, the condensed chromosomes appear to be BLM free. Because early cells seem to contain very little BLM, the conclusion is that BLM is another protein that is eliminated from the cell during late mitosis. Further research will be done in
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order to search for other proteins that localize with BLM using biochemical analysis of BLM.
Bloom’s syndrome is due to an error in the DNA repair system. DNA is damaged on a fairly regular basis in all individuals. This damage must be repaired by the cell in order for its continual existence. When a cell’s DNA is damaged, a number of systems will come into effect to repair the damage. Should these
systems fail, often the cell will simply die and will be of no further concern. In a small minority of cases, this damage may result in cancer. In Bloom’s Syndrome, the enzyme called DNA ligase is partially defective. DNA ligase is vital in DNA replication. A person without DNA ligase activity would not be viable, and would die early on at the fertilized egg stage. DNA ligase’s function is to seal up the DNA sugar-phosphate backbone. The DNA backbone gives the DNA structure, and describes its characteristic helical shape. When DNA is damaged, a number of enzymes will cut out the offending damage. After this, another enzyme called DNA polymerase will fill in the opposite side of the DNA strand. DNA ligase must reseal the backbone up the two strands. If DNA ligase cannot perform this function, as in the case of Bloom’s disease sufferers, the DNA will be unstable. Due to this, the DNA will become prone to further mutation.
Medical Treatment
There is no treatment for the underlying cause of Bloom’s Syndrome, and therefore medical intervention is primarily preventative. Adults with Bloom’s Syndrome should be more attentive than others in their surveillance of cancer. They
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should maintain close contact with a physician that has knowledge of the syndrome. They need to pay attention to symptoms that can be early evidence of a treatable pre-cancerous condition. Respiratory infections require prompt antibiotic treatment. Although growth hormone therapy has been attempted to increase height in children with Bloom’s Syndrome, it does not appear to be affective. In addition, there is some concern that the use of growth hormone may increase the risk for later malignancies.
The diagnosis of Bloom’s Syndrome can be confirmed or ruled out by a chromosome study. Blood and skin cells show a characteristic pattern of chromosome breakage and rearrangement. The gene mutation on chromosome fifteen has been identified as the cause of Bloom’s Syndrome. Because of these findings, both carrier testing and prenatal diagnosis for Bloom’s Syndrome are available.
A carrier screening requires a sample of blood. The test can determine whether or not a change is present in the gene for Bloom’s Syndrome. It is possible to detect the specific change that is seen in Ashkenazi Jews with Bloom’s Syndrome. The test is not as accurate for individuals who are from other ethnic backgrounds. Prenatal diagnosis for Bloom’s Syndrome can be attained with the use of CVS (chorion villus sampling), or amniocentesis. Both of which are performed early in the pregnancy.
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Advice For Couples That Are Carriers And The Phenotypic Appearances Of Offspring
Couples in which both individuals are carriers need to take precautions in their offspring’s health development in early stages of the pregnancy. When both the parents are carriers of Bloom’s syndrome, there is a twenty- five percent chance that their offspring will have the genetic disease each pregnancy. If both parents are carriers, it would be in the best interest if the mother participates in prenatal diagnosis. Although there is a risk of a miscarriage, the parents will be able to decide what is in their best interest in their situation.
Parents should become educated of the genetic disease if they choose to keep the child or unknowingly produce a child with this disease. It is in the best
interest of the child, for the parents to know of the disease and all of its effects. They should be aware of the physical appearances and health issues that their child is going to face. Close contact and a good relationship with a physician that has knowledge of the disease is essential.
The offspring with Bloom’s Syndrome will probably have redness on their face in a butterfly-like distribution. This factor is brought on by exposure to the sun. Crusting or even bleeding may occur due to their photosensitivity. Lack of the fat that normally develops in the facial area, contributes to the “birdlike” features such as a narrow face and prominent nose. The ears are relatively large and they also have a small mandible. The have long limbs and large hands and feet. They also have a very short stature and a high pitched voice.
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No specific treatment exists, but avoiding sun exposure and using sunscreen can help with the photosensitivity. Efforts to minimize exposure to other known environmental mutagens also are advisable. Consultation with dermatology for establishing the diagnosis, patient and family education, and sun protection guidance are a strongly advised. Health should be closely observed in order to diagnose early stages of treatable cancers.
Works Cited
Bloom’s
Syndrome
(Congenital Telangiectatic Erythema)
Danielle Dyan Parrington