He Bloom's syndrome (BS) is a rare autosomal recessive disease characterized primarily by three aspects: growth retardation, sun hypersensitivity and telangiectasia on the face (dilation of capillaries). These patients have genomic instability that predisposes them to develop cancer easily.
It was discovered by dermatologist David Bloom in 1954 through observation of several patients who had dwarfism and telangiectatic erythema (skin reddened by dilation of blood capillaries) (Elbendary, 2015).
This syndrome can also be called congenital telangiectasia erythema or Bloom-Torre-Machacek syndrome.
Causes of Bloom's syndrome
Bloom syndrome is an autosomal recessive disease, that is to say, a mutation has to occur in both alleles of the BLM gene, both by the mother and by the father (Ellis et al., 1995). Parents do not necessarily have to present this disease; they may be carriers of the mutated gene without having symptoms.
More than 60 mutations have been found in the BLM gene in Bloom syndrome, the most frequent being Deletion Of 6 nucleotides at position 2281 and substitution by other 7 (Elbendary, 2015).
According to the Genetics Home Reference (2016), the BLM gene is responsible for sending instructions for the creation of the RecQ protein, which is part of the Helicopters .
What the helicopters do is join the DNA And temporarily separating the two strands of the latter, which are normally spiral-bound, with the aim of developing processes such as replication (or DNA copy), preparation for cell division and repair of DNA damage.
In short, RecQ helicases are important for maintaining the structure of DNA and therefore are known as"caregivers of the genome".
For example, when a cell is to be divided to form two new cells, the DNA in the Chromosomes It must 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 has two equal structures called sister chromatids, and they are attached at the beginning, before the division of the cells takes place.
At this stage, they exchange some pieces of DNA between them; What is known as sister chromatid exchange. It appears that this process is altered in Bloom's disease, since the BLM protein is damaged and this is the one that controls the proper exchanges between the sister chromatids and that the DNA is stable at the time of the copy.
In fact, there is an average of 10 more than normal exchanges between chromatids in Bloom's syndrome (Seki et al., 2006).
On the other hand, there are also breakages in the genetic material in this disease, which cause deterioration in normal cellular activities that, due to the lack of BLM protein, can not be repaired.
In fact, some experts classify this syndrome as the"chromosomal breakage syndrome", as it is related to a large number of chromosome breaks and rearrangements.
This instability of the chromosomes causes a greater probability of developing diseases. For example, lack of BLM protein can not recover from DNA damage that can cause 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 by the uncontrolled division of cells, appearing mainly leukemia (It is a type of cancer of the blood characterized by an excess of white blood cells) and Lymphoma (Cancer of the lymph node of the immune system).
Failures have also been found in the action of the FANCM gene, which is responsible for the coding of MM1 and MM2 proteins, which also serve to repair DNA damage.
These are the ones that have been linked with both this syndrome and Fanconi anemia . That is why we see that these two diseases are similar in their phenotype and predisposition to hematological tumors and insufficiency in the bone marrow.
However, the molecular mechanisms that affect the chromosomes in Bloom's syndrome are still under investigation.
What is its prevalence?
Bloom's syndrome is relatively uncommon, only about 300 cases are known in the medical literature. 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, albeit less frequently, in Japanese families.
As for sex, men appear to be somewhat more likely to present the disease than women, with a ratio of 1.3 men to 1 woman.
What are your symptoms?
This condition is already present in the first months of life and, for now, none of the patients has lived more than 50 years.
- Malignant tumors : Caused by genomic instability as explained above, 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's syndrome will develop cancer. These patients have between 150 and 300 times more risk of developing cancer than people without this disorder.
- Immunodeficiency Which varies in severity according to the patient, and which 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 poor response to mitogen stimulation (which control cell division and growth).
- The Defects in T and B lymphocytes , Which affects the development of the immune system.
- He Malfunction of the immune system May result in ear infection (mainly otitis media), pneumonia Or other signs such as diarrhea and vomiting.
- Photosensitivity : Which is an excessive sensitivity of the DNA to the ultraviolet rays, getting to be damaged. It is considered a form of Phototoxicity Or cell death that damages the skin of the affected when it gives the sun.
- Reduced fertility or infertility . In fact, in males there is the inability to produce waiting. Menopause is very early in women.
- Skin manifestations : In addition to photosensitivity, poikiloderma also occurs, an involvement of the skin that occurs mainly in the neck, appearing hypopigmented areas, hyperpigmented areas, telangiectasia and atrophy. Red spots on the skin are commonly seen that are associated with sun exposure (especially on the face).
- Another skin problem observed is the Telangiectasia , Which is seen as reddish rashes on the face caused by dilation of small blood vessels. It appears as a"butterfly"pattern encompassing the nose and cheeks.
- They may also appear Abnormal brown spots Or gray in other parts of the body ("coffee-with-milk"stains).
- Developmental delay Which is already manifested in babies. The little ones usually have a distinctive head and face, narrower and smaller than normal.
- About 10% of those affected develop diabetes (National Organization for Rare Disorders, 2014).
- Very sharp voice .
- Alterations in teeth .
- Abnormalities of the eyes, ears (Prominent ears are observed), Hands or feet (Such as polydactyly, which occurs when the patient has more fingers than normal).
- Pilonidal cysts .
- Power Problems : They are especially noticeable in infants and young children, showing a lack of interest in eating. It is accompanied many times by severe gastroesophageal reflux.
- Intellectual abilities are variable , So that in some patients are more deteriorated and others are within the normal.
How is it diagnosed?
It can be diagnosed by any of the following tests:
- Cytogenetic tests Which measure chromosomal aberrations and the level of sister chromatid exchange.
The presence of quadri-radial associations (exchange of four-arm chromatids) in blood-lymphocytes can be observed, if there are high levels of exchange of sister chromatids in any cell, chromatid lagoons, ruptures or rearrangements; Or see directly whether there are mutations in the BLM gene.
These tests can detect a healthy individual who carries mutations in the BLM gene and can transmit them to their offspring.
The US Food and Drug Administration (FDA) announced in February of 2015 the commercialization of a genetic test for"23andMe"that may be useful to detect early the presence of this disease.
The presence of this syndrome should be suspected if these clinical conditions exist:
- Delay in significant growth Which is observed from the intrauterine period.
- Presence of erythema on the skin Of the face after exposure to the sun.
Do not confuse with...
Consider the following syndromes to rule them out before diagnosing Bloom's syndrome:
- Other autosomal recessive chromosomal instability syndromes Which 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 Which involve other genes and not BLM.
- Cockayne's Syndrome , Which consists of an inherited disorder manifested by developmental delay, photosensitivity and appearance aged at a young age. It is a rare form of dwarfism.
- Rothmund-Thomson syndrome : It is extremely rare and is manifested by typical abnormalities on the skin, hair defects, juvenile cataracts, short stature and skeletal alterations such as craniofacial malformations. It resembles Bloom's syndrome in inflammations of the skin, in poikiloderma, cutaneous degeneration (atrophy) and telangiectasias.
Treatment
There is no specific treatment for Bloom's syndrome, that is, for the excessive number of mutations. Rather, 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 the spots, redness and inflammation of the skin.
- Use antibiotics for infections.
- Periodic medical check-ups to detect possible cases of cancer, especially when these patients reach adulthood. It is necessary to try to be attentive to the possible symptoms, since there are tumors that for its recovery requires an early surgical subtraction. Some methods for the early diagnosis of cancer are mammography, PAP test Or vaginal cytology, or Colonoscopy .
- Control that these children receive the necessary nutrients trying to intervene the digestive reflux. For this, a tube can be placed in the upper part of the intestinal tract for a complementary feeding while sleeping. That may slightly increase small fat deposits, but it seems to have no effect on growth itself.
- Examine the existence of diabetes to treat it as soon as possible.
- If the individual has cancer, one can contemplate the bone marrow transplant .
- Family support and other groups and associations with similar diseases for the affected individual to develop as a person, with the greatest quality of life possible.
- If the family has had cases of this disease or the family of the spouse, genetic counseling would be useful to obtain information about the nature, inheritance, and consequences of this type of disorder to contribute to medical decision making And personal.
References
- Bloom syndrome . (S.f.). Retrieved on June 23, 2016, from Wikipedia.
- Bloom Syndrome . (2014). Retrieved on June 23, 2016, from the National Organization for Rare Disorders.
- Elbendary, A. (December 14, 2015). Bloom Syndrome (Congenital Telangiectatic Erythema) . Obtained from Medscape.
- Ellis, N.A., Groden, J., Ye T.Z., Straughen, J., Ciocci, S., Lennon, D.J., Proytcheva, M., Alhadeff, B., German, J. (1995). "The Bloom's syndrome gene is homologous to RecQ helicases." Cell 83: 655-666.
- German, J., & Sanz, M. & (S.f.). BLOOM'S SYNDROME. A descriptive summary prepared by the Bloom's Syndrome Registry for registered persons and their families. Retrieved on June 23, 2016, from BLOOM'S SYNDROME FOUNDATION.
- Sanz, M.G. (April 7, 2016). Bloom's Syndrome . Obtained from Gene Reviews.
- Seki, M., Nakagawa, T., Seki, T., et al. (2006). Bloom helicase and DNA topoisomerase III alpha are involved in the dissolution of sister chromatids. Mol Cell Biol .16: 6299-307.
- Image source .