The Bloom syndrome is a rare disease of autosomal recessive inheritance that is characterized mainly by three aspects: growth retardation, hypersensitivity to the sun and telangiectasia in the face (dilation of capillaries). These patients have genomic instability that predisposes them to easily develop cancer.
It was discovered by the dermatologist David Bloom in 1954 through the observation of several patients who presented dwarfism and telangiectatic erythema (reddened skin due to the dilation of blood capillaries).
This syndrome may also be called telangiectatic congenital erythema or Bloom-Torre-Machacek syndrome..
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Bloom syndrome is an autosomal recessive disease, that is, for it to arise, a mutation must occur in both alleles of the BLM gene, both by the mother and the father. Parents do not necessarily have to present this disease, but they can carry the mutated gene without having symptoms.
More than 60 mutations have been found in the BLM gene in Bloom syndrome, the most frequent being the deletion of 6 nucleotides at position 2281 and the substitution by another 7.
According to Genetics Home Reference, the BLM gene is responsible for sending instructions for the creation of the RecQ protein, which is part of the helicase family.
What helicases do is bind to DNA and temporarily separate its two strands, which are normally spirally linked, with the aim of developing processes such as replication (or DNA copying), preparation for cell division and repair. of DNA damage. In short, RecQ helicases are important to maintain the structure of DNA and that is why they are known as "genome keepers".
For example, when a cell is going to divide to form two new cells, the DNA on the chromosomes has to be copied so that each new cell has two copies of each chromosome: one from the father and one from the mother..
The DNA copied from each chromosome is arranged in two equal structures called sister chromatids, and they are joined at the beginning, before the cells divide..
At this stage, they exchange some pieces of DNA with each other; what is known as sister chromatid exchange. It seems that this process is altered in Bloom's disease, since the BLM protein is damaged and this is the one that controls that the appropriate exchanges take place between the sister chromatids and that the DNA remains stable at the time of copying. In fact, an average of 10 more than normal exchanges occurs between chromatids in Bloom syndrome..
On the other hand, breaks in the genetic material also originate in this disease, which cause deterioration in normal cellular activities that, due to the lack of the BLM protein, cannot be repaired.
Some experts classify this syndrome as the "chromosome break syndrome", since it is related to a large number of breaks and rearrangements of the chromosomes..
This instability of the chromosomes causes a greater probability of developing diseases. For example, due to the lack of the BLM protein, they cannot recover from DNA damage caused by ultraviolet light and therefore, these patients are photosensitive.
In addition, those affected have an immune deficiency that makes them more susceptible to infection. On the other hand, they have a high probability of developing cancer in any organ due to the uncontrolled division of cells, mainly appearing leukemia (it is a type of blood cancer characterized by an excess of white blood cells) and lymphoma (cancer in the lymph node of the system immune).
Failures have also been found in the action of the FANCM gene, which is responsible for encoding the MM1 and MM2 proteins, which also serve to repair DNA damage..
These are the ones that have been linked to both this syndrome and Fanconi anemia. That is why we see that these two diseases are similar in their phenotype and in their predisposition to hematological tumors and bone marrow failure..
However, the molecular mechanisms that affect chromosomes in Bloom syndrome are still under investigation..
Bloom syndrome is relatively rare, only about 300 cases described in the medical literature are known. Although this disorder occurs in many ethnic groups, it appears to be much more common in Ashkenazi Jews, accounting for 25% of patients with this syndrome..
In fact, within this ethnic group the frequency of presenting the syndrome can reach 1%. It has also been found, although less frequently, in Japanese families.
Regarding sex, men seem to be somewhat more likely to present the disease than women, with the ratio being 1.3 men for 1 woman.
This condition already occurs in the first months of life and, for now, none of the patients have lived more than 50 years.
Caused by genomic instability as explained above, they are the main reason for death in those affected by this syndrome. According to the National Organization for Rare Disorders (2014), about 20% of those affected by Bloom syndrome will develop cancer. These patients are 150 to 300 times more at risk of developing cancer than people without this disorder.
It varies in severity depending on the patient and predisposes to various infections. This arises from deficits in the proliferation of lymphocytes (white blood cells), problems in the synthesis of immunoglobulin (antibodies of the immune system) and a low response to stimulation by mitogens (which control the division and growth of cells)..
Defects in T and B lymphocytes are common, affecting the development of the immune system. Malfunction of the immune system can lead to ear infection (mainly otitis media), pneumonia or other signs such as diarrhea and vomiting.
It is an excessive sensitivity of DNA to ultraviolet rays, becoming damaged. It is considered a form of phototoxicity or cell death that damages the skin of the affected person when it hits the sun.
In males there is the inability to produce waiting. Very early menopause occurs in women.
In addition to photosensitivity, there is also poikiloderma, an affection of the skin that occurs mainly in the neck, appearing hypopigmented areas, other hyperpigmented areas, telangiectasias and atrophy. Red patches on the skin are commonly seen associated with sun exposure (especially on the face).
Another skin problem seen is telangiectasia, which is seen as reddish rashes on the face caused by the dilation of small blood vessels. Appears as a "butterfly" pattern spanning the nose and cheeks.
Abnormal brown or gray spots may also appear on other parts of the body (“café au lait” spots)..
Developmental delay already manifested in babies. The little ones usually have a distinctive head and face, narrower and smaller than normal..
- About 10% of those affected end up developing diabetes.
- Very high-pitched voice.
- Tooth alterations.
- Abnormalities in the eyes, ears (prominent ears are seen), hands or feet (such as polydactyly, which occurs when the patient has more fingers than normal).
- Pilonidal cysts.
- Feeding problems: they are noticed especially in babies and young children, showing a lack of interest in eating. It is often accompanied by severe gastroesophageal reflux.
- Intellectual abilities are variable, so that in some patients they are more impaired and in others they are within normal limits..
It can be diagnosed by any of the following tests:
Measure chromosomal aberrations and the level of sister chromatid exchange.
It is possible to observe the presence of quadri-radial associations (exchange of chromatids of four arms) in lymphocytes cultured in blood, look for high levels of exchange of sister chromatids in any cell, chromatid gaps, breaks or rearrangements; or, see directly if there are mutations in the BLM gene.
These tests can detect a healthy individual who carries mutations in the BLM gene and can pass them on to their offspring..
The United States Food and Drug Administration (FDA) announced in February 2015 the commercialization of a genetic test for “23andMe” that may be useful to detect the presence of this disease early..
The presence of this syndrome should be suspected if these clinical conditions exist:
- Significant growth delay seen from the intrauterine period.
- Presence of erythema on the skin of the face after exposure to the sun.
The following syndromes must be considered to rule out before diagnosing Bloom syndrome:
They are linked to breaks and rearrangements of chromosomes, making the subject especially vulnerable to certain types of cancer such as: Fanconi anemia, ataxia telangiectasia or xeroderma pigmentosa that involve other genes and not BLM.
It consists of an inherited disorder that manifests itself by delayed development, photosensitivity and an aged appearance at a young age. It is a rare form of dwarfism.
It is extremely rare and is manifested by typical skin abnormalities, hair defects, juvenile cataracts, short stature, and skeletal abnormalities such as craniofacial malformations..
It resembles Bloom syndrome in skin inflammations, poikiloderma, skin degeneration (atrophy) and telangiectasias.
There is no specific treatment for Bloom syndrome, that is, for the excessive number of mutations. Rather, the interventions are aimed at alleviating symptoms, offering support and preventing complications.
- Try not to expose yourself directly in the sun.
- Use a suitable sunscreen.
- Follow-up by a dermatologist, to treat spots, redness and inflammation of the skin.
- Using antibiotics for infections.
- Periodic medical check-ups to detect possible cases of cancer, mainly when these patients reach adulthood. We must try to be attentive to possible symptoms, since there are tumors that require an early surgical removal for their recovery. Some methods for the early diagnosis of cancer are mammography, Pap smear or Pap smear, or colonoscopy..
- Control that these children receive the necessary nutrients trying to intervene digestive reflux. To do this, a tube can be placed in the upper part of the intestinal tract for complementary feeding while you sleep. That may increase the fat deposits of the little ones a bit, but does not seem to have an effect on growth itself..
- Screen for diabetes to treat it as soon as possible.
- If the individual has cancer, bone marrow transplantation may be considered.
- Family support and from other groups and associations with similar diseases so that the affected individual develops as a person, with the highest possible quality of life.
- If cases of this disease have been had in the family or by the spouse's family, genetic counseling would be useful to obtain information on the nature, inheritance, and consequences of this type of disorder to contribute to medical decision-making and personal.
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