Bloom’s Syndrome (BS) is a rare autosomal recessive disorder characterized by photosensitivity, growth deficiency of prenatal onset, variable degree of immunodeficiency, and increased susceptability to neoplasms of many sites and types. Bloom’s Syndrome is also known as Congenital Telangiectatic Erythema. Bloom’s Syndrome is an inherited condition, which means that it is passed from parents to offspring. Bloom’s Syndrome is caused by a gene that does not function properly. Individuals with Bloom’s Syndrome have an unusually high number of breaks along their chromosomes. A chromosome is a structure in our body that contains DNA-genetic material.
History and Background Bloom’s Syndrome was first described by New York Dermatologist David Bloom in 1954. Since then, over 170 individuals have been recognized as being affected. Because Bloom’s Syndrome is inherited as an autosomal recessive disease, once a couple has an affected child, there is a one in four (twenty-five Parrington 2 percent) chance for affected offspring in all future pregnancies. The gene mutation is very rare in most populations. The gene mutation is more frequent among Ashkenazi Jews, where the carrier rate may be greater than 1 out of 110, approximately one percent. Carriers of Bloom’s Syndrome do not manifest symptoms of the disease.
Individuals affected with Bloom’s Syndrome have inherited two copies of the Bloom’s Syndrome gene mutation. Typically they have certain features which don’t look phenotypically normal. Most individuals are of an unusually small size at birth but otherwise have a normal degree of maturation. Most have a very short stature after birth, only rarely reaching five feet in height. There is a redness of the skin on the face, mainly the lower eyelids, the bridge of the nose and the adjoining upper cheek area, and the lower lip. There are increased numbers of respiratory tract and ear infections, some of which can be life threatening.
The skin problem, which is aggravated by sun exposure (photosensitivity), varies in severity. It may be quite disfiguring in some affected individuals, but very mild or even absent in others, however the skin condition improves with age. Bloom’s syndrome is usually associated with dwarfism. Diabetes occurs in approximately ten percent of individuals with Bloom’s Syndrome. Intelligence is usually normal, although mild mental deficiency has occurred in a few affected persons.
Men with Bloom’s Syndrome are usually infertile, and fertility appears to be reduced in women affected with Bloom’s Syndrome. The risk of cancer is greater than normal throughout life. The variety of sites and types that affect the general population. 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 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 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.