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NORD is very grateful to John Barranger, PhD, MD, Director, Lysosomal Storage Disease, Clinical Care Network, for assistance in the preparation of this report.
Bloom syndrome is a rare genetic disorder characterized by short stature; increased sensitivity to light (photosensitivity); multiple small dilated blood vessels on the face (facial telangiectasia), often resembling a butterfly in shape; immune deficiency leading to increased susceptibility to infections; and, perhaps most Importantly, a markedly increased susceptibility to cancer of any organ, but especially to leukemia and lymphoma. Some clinicians classify Bloom syndrome as a chromosomal breakage syndrome; that is, a disorder associated with a high frequency of chromosomal breaks and rearrangements. It is suspected that there is a link between the frequency of chromosomal breaks and the increased propensity toward malignancies.
Bloom syndrome is inherited as an autosomal recessive genetic trait. It is often included among the Jewish genetic diseases.
Infants and adults with Bloom syndrome are atypically small with normal body proportions. Affected infants and children usually present with a distinctive, narrow, small head and face. Sometimes, these signs are accompanied by a reddish facial rash that is due to the dilation of very small blood vessels (telangiectasia) of the face. The rash typically appears in a "butterfly" pattern on the cheeks and across the nose. Areas of abnormal brown or gray skin coloration (cafe-au-lait spots) may occur on other parts of the body. The skin is highly sensitive to sun and light (photosensitive) and may become very red upon exposure, especially on the face.
Approximately 50 percent of people with this disorder eventually develop any one of a variety of malignancies, especially leukemia and squamous cell cancer of the skin. About 10 percent of the people who have Bloom syndrome will develop diabetes as well.
Male sterility is not uncommon because, for reasons that are not yet well understood, affected males are unable to produce sperm. Female infertility is not uncommon because menstruation ceases at an abnormally early age among affected females.
Also, people with Bloom syndrome typically have abnormalities of the immune system that often result in inner ear infections (otitis media) and/or pneumonia. Other symptoms may include diarrhea and vomiting.
In addition, affected individuals may have a characteristically high-pitched voice, dental abnormalities, prominent ears, cysts at the base of the spine (pilonidal), and/or extra fingers (polydactyly). Occasionally, other abnormalities of the eyes, ears, hands, and/or feet may also be present.
Bloom syndrome is inherited as an autosomal recessive genetic trait. The defective gene has been mapped to chromosomal locus 15q26.1 and is responsible for encoding a protein known as BLM. A single mutation, known as BLMASH, is responsible for almost all cases of Bloom syndrome among Ashkenazi Jews.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 11p13" refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic 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 usually will 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.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Bloom syndrome is of special interest to geneticists because patients with this disorder bear chromosomes that are highly unstable so that mutations are frequently encountered. In addition, the recombination of chromosomes of such patients occurs with much greater frequency and apparently with much greater ease than normal. Most clinicians engaged in studies of Bloom syndrome consider the volatility of the chromosomes to be a major contributor to both short stature and a predisposition to cancerous growth.
Geneticists and genetic counselors label such chromosomal recombinations as sister-chromatid exchange (SCE). This phrase means that portions of the chromosomal-DNA are exchanged among paired (sister) chromosomes. Bloom syndrome is the striking example of this phenomenon and, since the exchange is made visible under certain circumstances, the presence of multiple SCEs may be a diagnostic indicator.
Clinical researchers consider the protein (a helicase) controlled by the gene for Bloom syndrome to be involved in cell repair, cell division, and cell death. Bloom syndrome is presumed to result from a defect of the cell's DNA repair system. DNA may be damaged during the course of a cell's life and must be repaired if the cell is to continue to function. If DNA repair is inhibited, the cells will die and be replaced by another. However, in some cases the damage may result in malignancies.
Bloom syndrome is rare; with about 200 cases reported. Although this disorder occurs in many ethnic groups, it is more prevalent in people of Ashkenazi Jewish heritage whose ancestors were from Poland or the Ukraine. Among Ashkenazi Jews, the carrier frequency for Bloom syndrome is about 1%. Another, but smaller, cluster of cases is found among Japanese families.
Bloom syndrome patients seem to have 150-300 times the risk of developing cancerous growths as do people without this disorder. About 20% of Bloom syndrome patients will develop malignancies. There also appears to be a slightly greater propensity for males than for females to have this disorder.
Symptoms of the following disorders can be similar to those of Bloom syndrome. Comparisons may be useful for a differential diagnosis:
Chromosomal Instability syndromes are autosomal recessive inherited disorders that are associated with increased chromosomal breakage and genetic instability. These chromosomal changes place affected individuals at a higher than average risk for certain cancers, especially leukemia. Chromosomal Instability syndromes include Fanconi's anemia, ataxia telangiectasia, and xeroderma pigmentosum. (For more information on these disorders choose "Fanconi," "Ataxia Telangiectasia," and "Xeroderma Pigmentosum" as your search terms in the Rare Disease Database.)
Cockayne syndrome (CS) is a rare form of dwarfism. It is an inherited disorder the diagnosis of which depends on the presence of three signs: growth retardation, abnormal sensitivity to light (photosensitivity), and 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. A fourth form, now recognized as xeroderma pigmentosa-Cockayne syndrome (XP-CS), combines features of both of these disorders. (For more information on this disorder choose "Cockayne Syndrome" as your search term in the Rare Disease Database.)
Rothmund-Thomson syndrome is an extremely rare inherited, multisystem disorder that is usually apparent during early infancy. The disorder is typically characterized by distinctive abnormalities of the skin, defects of the hair, clouding of the lenses of the eyes (juvenile cataracts), short stature and other skeletal abnormalities, malformations of the head and facial (craniofacial) area, and other physical abnormalities. In rare cases, mental retardation may be present. The range and severity of symptoms may vary from case to case.
During early infancy, individuals with Rothmund-Thomson syndrome develop red, inflamed patches (plaques) on the skin (erythema) accompanied by abnormal accumulations of fluid between layers of tissue under the skin (edema). Such plaques typically first appear on the cheeks. In most cases, additional areas of the skin may then become involved to a lesser degree (e.g., the skin of the ears, forehead, chin, hands, forearms, and lower legs). Inflammation eventually tends to recede and the skin of affected areas develops a condition known as poikiloderma, characterized by abnormal widening (dilation) of groups of small blood vessels (telangiectasia); skin tissue degeneration (atrophy); and patchy areas of abnormally decreased and/or unusually increased pigmentation (depigmentation and hyperpigmentation). In many cases, additional skin abnormalities may also occur. (For more information on this disorder choose "Rothmund-Thomson," as your search terms in the Rare Disease Database.)
The treatment of Bloom syndrome is symptomatic and supportive. Sunscreens may be used and affected individuals should avoid contact with direct sunlight. Periodic evaluation by a dermatologist is also advised. Infections may be treated aggressively with antibiotic drugs. Physicians must be conscientious in watching for indications of cancer, especially with patients who reach adulthood.
Genetic counseling may be of benefit for people with Bloom syndrome and their families.
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:
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Contact for additional information about Bloom syndrome:
John Barranger, PhD, MD
Director, Lysosomal Storage Disease, Clinical Care Network
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Report last updated: 2011/03/10 00:00:00 GMT+0