It is a prototype for a group of genetic conditions known as chromosome break syndromes.
Bloom syndrome is a rare genetic disorder characterized by short stature, increased sensitivity of the skin to the sun’s ultraviolet rays, and multiple small, dilated blood vessels on the nose and cheeks that resemble the shape of a butterfly.
In addition, this disorder presents mild immunodeficiency with greater susceptibility to infections; and, most importantly, a marked increase in exposure to many types of cancer, especially leukemia, lymphoma, and tumors of the gastrointestinal tract.
The genetic abnormality in Bloom syndrome causes problems with DNA repair, resulting in a high number of chromosome breaks and rearrangements. Abnormal DNA repair is responsible for the increased risk of cancer.
Bloom syndrome is inherited as an autosomal recessive genetic trait. It is often included among Jewish genetic diseases.
Signs and symptoms
Babies and adults with Bloom syndrome are short and underweight and have a small head circumference but have normal body proportions. Affected infants and children usually present a distinctive, narrow, small head and face.
Sometimes these signs are accompanied by a reddish facial rash due to the dilation of tiny blood vessels in the face. The rash typically appears in a “butterfly” pattern on the cheeks and nose.
Certain areas of abnormal brown or gray skin coloration (café-au-lait spots) can occur in other body parts. The skin is susceptible to sunlight (photosensitive) and can become very red when exposed, especially on the face.
At least 50% of people with this disorder eventually develop a variety of malignant tumors, especially leukemia and cancer of the gastrointestinal tract, such as the colon. About 10% of people who have Bloom syndrome will also develop diabetes.
Male infertility is expected because, for reasons that are not well understood, men with Bloom syndrome cannot 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 generally have abnormalities in the immune system that often increase the number of middle ear infections (otitis media) and pneumonia.
Many people with Bloom syndrome have a characteristically high voice, dental abnormalities, prominent ears, cysts at the base of the spine (pilonidal), and extra fingers (polydactyly). Occasionally, other anomalies of the eyes, ears, hands, and feet may also be present.
Bloom syndrome is inherited as an autosomal recessive genetic trait. The causative gene has been mapped to the 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 of each individual. Cells in the human body usually have 46 chromosomes.
Human chromosome pairs are numbered 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 as “p” and a long arm designated as “q.”
Chromosomes are subdivided 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 present on each chromosome.
Genetic diseases are caused by the combination of genes for a particular trait that is found on the chromosomes received from the father and mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives a normal gene and a gene for the disease, the person will be a carrier of the disease but usually will not have symptoms.
The risk of two carrier parents passing the disease-causing gene and thus having an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy.
The chance that a child will receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for men and women.
All individuals carry some abnormal genes. Parents who are close relatives (blood) are more likely than unrelated parents to both have the same abnormal gene, increasing the risk of having children with a recessive genetic disorder.
Bloom syndrome is of particular interest to geneticists because patients with this condition have unstable chromosomes, so mutations are frequently found.
Furthermore, recombination of chromosomes from such patients occurs much more frequently and quickly than usual.
Chromosome volatility is considered a significant contributor to short stature and a predisposition to cancer by most clinicians involved in studies of Bloom syndrome.
Bloom syndrome is rare, with approximately 275 reported cases. Although it occurs in many ethnic groups, it is more common in people of Ashkenazi Jewish heritage whose ancestors were from Poland or Ukraine.
Among Ashkenazi Jews, Bloom syndrome carriers’ frequency is approximately 1 in 100. However, Bloom syndrome has been seen in many other people worldwide, and approximately 75% of cases occur in people. They are not of Jewish descent.
People with Bloom syndrome appear to have between 150 and 300 times the risk of developing cancerous tumors than people without this disorder. Most people with Bloom syndrome are likely to develop cancer throughout their lives.
The symptoms of the following disorders may be similar to those of Bloom syndrome. Comparisons can be helpful for a differential diagnosis:
Chromosome instability syndromes are inherited autosomal recessive disorders associated with increased chromosome breakage and genetic instability.
These chromosomal changes put affected people at higher than average risk for certain cancers, especially leukemia. Chromosome instability syndromes include Fanconi anemia, ataxia-telangiectasia, and xeroderma pigmentosum.
Cockayne syndrome is a variable genetic condition with cardinal features of growth failure and progressive neurological deterioration. In the classic form of Cockayne syndrome, growth and neurological problems usually manifest after one year.
A more severe form of Cockayne syndrome is evident at birth (congenital) or in the early neonatal period.
There is a third form, known as Type III Cockayne syndrome, which occurs later in the child’s development and is generally a milder form.
A fourth form, now recognized as xeroderma pigmentosa-Cockayne syndrome, combines features of these two disorders.
Rothmund-Thomson syndrome is a multisystemic genetic disorder that usually manifests during early childhood. It is characterized by distinctive skin abnormalities, scant or abnormal hair texture, clouding of the eye lenses, short stature, and other skeletal abnormalities such as absent or irregular thumbs.
How is Bloom syndrome treated?
There is no cure for Bloom syndrome. Children with Bloom syndrome need nutritional monitoring to ensure maximum growth.
People with the disease are advised to stay out of the sun and use sunscreen to avoid skin injury, especially during childhood. They must also make an effort to prevent infections of all kinds. At school, they may require special education classes due to learning difficulties.
People with Bloom syndrome are prone to cancer, so they should be screened regularly beginning in childhood and increased surveillance into adulthood.
Standard cancer treatments often need to be modified because they are susceptible to radiation and DNA-damaging chemicals. If diabetes is present, this condition is usually treated with diet, blood sugar control, and insulin supplementation.
What is the prognosis?
Despite dealing with numerous medical problems, people with Bloom syndrome can lead productive lives. More often, they are of average or near-normal intelligence.
People with Bloom syndrome generally have shorter lives, although life expectancy can vary significantly from person to person. The cause of death is usually cancer, which can occur in childhood, but most commonly appears in the late teens or early to mid-twenties.