Bloom syndrome is a genetic disorder, rare and characterized by a small stature; heightened photosensitivity which means increased skin sensitivity to ultraviolet rays of the sun; several small amplified blood vessels known as telangiectasia scattered around the cheek and nose and cheeks with a butterfly-like shape, slight immune deficiency with intensified susceptibility to infections and many types of cancer, particularly lymphoma, gastrointestinal tract tumor, leukemia.
Bloom syndrome is an original type of a group of congenital conditions known as chromosome breakage syndromes.
The genetic anomaly in Bloom syndrome causes difficulties with DNA repair, which allows a substantial amount of chromosome breaks and rearrange. The problem of DNA repair is responsible for the heightened risk of cancer.
Bloom syndrome is hereditary as an autosomal recessive genetic trait. It is considered a part of Jewish genetic diseases.
Signs & Symptoms
Infants and adults with Bloom syndrome are usually underweight and short with smaller than average head circumference, although with normal body proportions.
Infants and children affected by the bloom syndrome typically have an unusual, thin, little head and face. Other times, these signs are also followed by a facial rash reddish in the color that is as a result of the dilation of tiny blood vessels (telangiectasia) of the face.
The rash generally forms a butterfly-like pattern across the nose and cheeks. Sites of anomalous gray or brown skin coloration (cafe-au-lait spots) may emerge on other body parts. The skin is hypersensitive to sunlight and can become very red when exposes, especially on the face.
At least more than 51% of people with the bloom disorder ultimately develop at least one type of malignancies, particularly cancers of the gastrointestinal tract such as the pancreas, rectum, or colon or leukemia. Studies have shown over 10% of people with Bloom syndrome will develop diabetes also.
Male infertility is prevalent because, for reasons that are not fully understood by scientists, men with Bloom syndrome are incapable of sperm production. At the same time, Female infertility is also common because menstruation stops at an early age among women with Bloom syndrome.
Furthermore, people with Bloom syndrome generally have irregularities of the immune system that frequently stem in an increased case of pneumonia and/or middle ear infections (otitis media).
Many persons with Bloom syndrome are attributed with Polydactyly ( extra fingers), dental irregularities, pilonidal
(cysts at the base of the backbone), high-pitched voice, prominent ears. Sometimes, other abnormalities can be seen on the feet, ears, hands, or/and eyes.
Causes
Bloom syndrome is received as an autosomal recessive genetic trait. The gene can cause this has been identified to be the chromosomal locus 15q26.1 and is liable for encoding a protein known as BLM.
This single mutation, called BLMAsh, is accountable for over 50% of all cases of Bloom syndrome, which is common among Ashkenazi Jews.
Chromosomes, which can be referred to as a genetic carrier, holds the genetic information for every individual.
Human body cells typically have 46 chromosomes. A Pair of human chromosomes are numbered from 1 through 22, and the sex chromosomes are known as X and Y. Men possess one X and one Y chromosome, while women have a pair of X chromosomes. Every chromosome has a short arm identified “p,” and a long arm designated “q.”
Genetic conditions are a result of the fusion of genes for specific traits found inside the chromosome.
Recessive genetic disorders happen when a child receives the same abnormal gene for the same trait, respectively, from both parents.
If a person obtains one normal gene and another one for a disease, the child will be a disease carrier but usually will not show any signs or symptoms. The implication for both carrier parents to pass the disease-causing gene and, therefore, to have an affected child is over 25 percent with every pregnancy.
The odds of having a child who is a carrier like the parents is 50% with every conception. The risk for a child to receive non-carrier genes from both father and mother and become genetically normal for that particular trait of disease is 25%. The chances are the same for males and females.
Every individual has some abnormal genes. Especially when Parents who are closely related (consanguineous), which increases the chances in (comparison to unrelated parents to both carry the same anomalous gene), which raises the risk of having offsprings with a recessive genetic disorder.
Bloom syndrome is of interest to geneticists because patients with this condition have chromosomes that are so highly unstable that mutations are frequently encountered.
Complementarily, the recombination of chromosomes of such patients occurs with much higher frequency and seemingly with much greater ease than usual.
Most clinicians who carry out studies on Bloom syndrome consider the volatility of the chromosomes to significantly contribute to both short stature and susceptibility to cancer.
One of the classes of chromosomal integration that happens in Bloom syndrome is called sister-chromatid exchange (SCE), which means that parts of the chromosomal-DNA are traded among paired (sister) chromosomes.
Bloom syndrome is the only human genetic disease in which cells undergo increased levels of SCE. Because these SCE’s can be seen under the microscope, the presence of multiple SCE’s is a diagnostic indicator.
The protein regulated by the gene for Bloom syndrome is required in cell division, cell repair, and cell death.
Bloom syndrome is believed to result from a defect of the cell’s DNA repair system. DNA may be damaged during a cell’s life and must be repaired if the cell is to continue to function.
If the damaged DNA is not repaired correctly, the cells may die and be replaced by others; or in other cases, the damaged cells may proceed to grow abnormally and result in cancer.
Affected Populations
Bloom syndrome is not common; annually, about 275 cases are reported. Although it emerges in different ethnic groups, it is more common in people of Ashkenazi Jewish heritage whose ancestors were from Ukraine or Poland.
Among Ashkenazi Jews, the carrier rate for Bloom syndrome is about 1 in 100. Bloom syndrome has been observed in many other persons globally. However, 75% of cases exist in people who are not of Jewish ancestry.
People with Bloom syndrome appear to have over 300 times more risk of having cancerous growths. So over half the population of people with Bloom syndrome are likely to get cancer over their lifetimes.
Related Disorders
Symptoms of the below-listed disorders can be similar to those of Bloom syndrome, and comparing them may be useful for a differential diagnosis:
Chromosomal abnormality syndromes are autosomal recessive inherent diseases that are linked with enhanced chromosomal breakage and genetic fluctuations.
These chromosomal alterations position affected individuals at a higher than normal risk for certain cancers, especially leukemia. Chromosomal abnormality syndromes include Xeroderma pigmentosum, Fanconi anemia, and ataxia-telangiectasia.
Cockayne syndrome (CS) is a varying congenital condition with primary indications of growth deficiency and advancing neurological erosion. In the original variety of Cockayne syndrome (CS type I), the advancement and neurological problems generally become evident after the age of one year.
A more severe form of Cockayne syndrome (CS type II) is noticeable at birth (congenital) or in the early newborn period. There is a third variety, known as Cockayne syndrome Type III (CS type III), that becomes evident later in the child’s growth and is considered a milder form.
A fourth variety, now called xeroderma pigmentosa-Cockayne syndrome (XP-CS), incorporates characteristics of both of these disorders.
Rothmund-Thomson syndrome is also a genetic disorder that affects more than one body system, usually noticeable during early infancy.
It is distinguished by Abnormal or sparse hair texture, Juvenile cataracts, poikiloderma i.e. distinctive aberrations of the skin and additional skeletal abnormalities such as a missing or malformed thumb.
During stages of early infancy, children with Rothmund-Thomson can develop inflamed reddish patches (plaques) on the skin along with abnormal assemblages of fluid between layers of tissue underneath the skin.
These plaques may typically appear on the cheeks. However, other parts of the skin may then become affected to a minor degree (e.g., the surface of the lower legs, forearms, hands chin ears, forehead) Inflammation ultimately tend to ebb, and the skin of the areas develops poikiloderma, distinguished by unusual dilation of groups of small blood vessels (telangiectasia); atrophy; and patchy body sites of anomalous reduction and/or unusually heightened pigmentation (known as depigmentation and hyperpigmentation).
In numerous cases, additional skin abnormalities may occur.
Treatment and management
The treatment option of Bloom syndrome is symptomatic and supportive. Physicians must be ethical and conscious in monitoring signs indicating cancer, especially with patients who have reached adulthood following recommendations for cancer surveillance.
Due to hypersensitivity of patients to chemotherapy, reduced dosage and/or duration of therapy is recommended, usually beginning with 50% of the weight-based dosage.
Caution should be exercised with the use of ionizing radiation or alkylating agents, particularly busulfan, cyclophosphamide or melphalan.
Increased calorie density formulas and foods may facilitate weight gain and improved growth.
Although growth hormone treatment can also enhance linear growth, many clinicians advise against its use because of reports of the early development of cancer in some children treated with the growth hormone therapy.
Infections should be treated aggressively with antibiotic medications. When the levels of immunoglobulins are low, and the patient is suffering from reoccurring infections, it could be treated with intravenous or subcutaneous immunoglobulins.
Sunscreens may be applied and used to lessen exposure to UV radiation, and persons with Bloom syndrome should avoid contact with direct sunlight. Occasional examination by a dermatologist is also advised.
Sun protection, including covering all exposed skin and the use of a broad-spectrum sunscreen with a minimum of 30 SPF, is significant to lessen the sun-sensitive skin rash.
Genetic counseling may be of benefit for persons with Bloom syndrome as well as their families.
