NORD gratefully acknowledges Chris Cunniff, MD, Director of the Bloom’s Syndrome Registry, and Amir R. Djavid, BA, Research Assistant at the Bloom’s Syndrome Registry, for assistance in the preparation of this report.
Bloom syndrome is a rare genetic disorder characterized by short stature; increased skin sensitivity to ultraviolet rays from the sun (photosensitivity); multiple small dilated blood vessels (telangiectasia) over the nose and cheeks resembling a butterfly in shape; mild immune deficiency with increased susceptibility to infections; and most importantly, a markedly increased susceptibility to many types of cancer, especially leukemia, lymphoma and gastrointestinal tract tumors. Bloom syndrome is a prototype of a group of genetic conditions known as chromosome breakage syndromes. The genetic abnormality in Bloom syndrome causes problems with DNA repair, resulting in a high number of chromosome breaks and rearrangements. The abnormal DNA repair is responsible for the increased risk for cancer.
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 short and underweight and have a small head circumference, but they have 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 sunlight (photosensitive) and may become very red upon exposure, especially on the face.
At least 50% of people with this disorder eventually develop any one of a variety of malignancies, especially leukemia and cancers of the gastrointestinal tract such as the colon. About 10% of people who have Bloom syndrome will develop diabetes as well.
Male sterility is common because, for reasons that are not well understood, men with Bloom syndrome are unable to produce sperm. Female infertility is also common because menstruation ceases at an abnormally early age among women with Bloom syndrome.
Also, people with Bloom syndrome typically have abnormalities of the immune system that often result in an increased number of middle ear infections (otitis media) and/or pneumonia.
Many persons with Bloom syndrome 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 causative 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 nuclei 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 15q26.1” refers to band 26.1 on the short arm of chromosome 15. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are caused 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 disease-causing gene and therefore to 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 condition 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 seemingly 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 cancer.
One of the types of chromosomal recombination that occurs in Bloom syndrome is known as sister-chromatid exchange (SCE). This means that portions of the chromosomal-DNA are exchanged among paired (sister) chromosomes. Bloom syndrome is the only known human genetic condition in which cells undergo high levels of SCE; and because these SCE’s can be viewed under the microscope, the presence of multiple SCE’s is a diagnostic indicator.
The protein (a RecQ helicase) controlled by the gene for Bloom syndrome is 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 the damaged DNA is not repaired properly, the cells may die and be replaced by others; or in some cases the damaged cells may continue to grow in an abnormal fashion and result in cancer.
Bloom syndrome is rare; with about 275 cases reported. Although it 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 in 100. Bloom syndrome has been seen in many other persons from throughout the world however, and about 75% of cases occur in people who are not of Jewish ancestry.
People with Bloom syndrome appear to have 150-300 times the risk of developing cancerous growths as do people without this disorder. Most people with Bloom syndrome are likely to develop cancer over their lifetimes.
The treatment of Bloom syndrome is symptomatic and supportive. Sunscreens may be used to decrease exposure to UV radiation, and persons with Bloom syndrome should limit 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.
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