BLOOM SYNDROME: SYMPTOMS, CAUSES AND TREATMENT - NEUROPSYCHOLOGY - 2025

The Bloom syndrome is a rare disease of autosomal recessive mainly characterized by three aspects: stunting, hypersensitivity to the sun and on the face telangiectasia (dilation of capillaries). These patients have genomic instability that predisposes them to easily develop cancer.

It was discovered by dermatologist David Bloom in 1954 through the observation of several patients with 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.

Causes of Bloom syndrome

Bloom syndrome is an autosomal recessive disease, that is, for it to arise, a mutation has to occur in both alleles of the BLM gene, both by the mother and the father. Parents do not necessarily have to have 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.

Gen BLM and helicases

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 the two strands of it, which are normally linked in a spiral, with the aim of developing processes such as replication (or DNA copy), preparation for cell division and repair. of DNA damage. Ultimately, RecQ helicases are important for maintaining DNA structure and are therefore 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 copied DNA of each chromosome has two identical 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.

Breakdown of genetic material

On the other hand, breaks in the genetic material are also caused 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", as it is related to a large number of breaks and rearrangements of chromosomes.

High incidence of disease

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 that can be caused by ultraviolet light and therefore, these patients are photosensitive.

In addition, those affected have an immune deficiency that makes them more susceptible to contracting infections. 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).

Gen FANCM

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.

What is its prevalence?

Bloom syndrome is relatively uncommon, 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.

Symptoms

This condition already occurs in the first months of life and, for now, none of the patients have lived more than 50 years.

Malignant tumors

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 have 150 to 300 times the risk of developing cancer than people without the disorder.

Immunodeficiency

Defects in T and B lymphocytes are common, affecting the development of the immune system. The malfunction of the immune system can lead to ear infection (mainly otitis media), pneumonia or other signs such as diarrhea and vomiting.

Photosensitivity

It is an excessive sensitivity of DNA to ultraviolet rays, leading to damage. It is considered a form of phototoxicity or cell death that damages the skin of the affected person when it hits the sun.

Reduced fertility or infertility

In males there is the inability to produce waiting. In women there is a very early menopause.

Cutaneous manifestations

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).

Telangiectasia

Another skin problem seen is telangiectasia, which is seen as reddish rashes on the face caused by the dilation of small blood vessels. It appears as a "butterfly" pattern encompassing the nose and cheeks.

Spots

Abnormal brown or gray spots may also appear on other parts of the body (“café au lait” spots).

Developmental problems

Developmental delay that is already manifested in babies. The little ones usually have a distinctive head and face, narrower and smaller than normal.

Others

- About 10% of those affected end up developing diabetes.

- Very high-pitched voice.

- Alterations in the teeth.

- Abnormalities in 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.

- 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.

Diagnosis

It can be diagnosed by any of the following tests:

Cytogenetic tests

They measure chromosomal aberrations and the level of sister chromatid exchange.

It is possible to observe the presence of quadri-radial associations (exchange of four-arm chromatids) in lymphocytes cultured in blood, to see if there are 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 US 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 delay in growth observed from the intrauterine period.

- Presence of erythema on the skin of the face after exposure to the sun.

Do not confuse with…

The following syndromes should be considered to rule out before diagnosing Bloom syndrome:

Other autosomal recessive chromosomal instability syndromes

It consists of an inherited disorder that is manifested by delayed development, photosensitivity and an aged appearance at a young age. It is a rare form of dwarfism.

Rothmund-Thomson syndrome

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.

Treatment

There is no specific treatment for Bloom 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 under the sun.

- Use a suitable sunscreen.

- Follow-up by a dermatologist, to treat spots, redness and inflammation of the skin.

- Use 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.

- Check 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 can increase the fat stores of the little ones a bit, but does not seem to have an effect on growth itself.

- Examine the existence of diabetes to treat it as soon as possible.

- If the individual has cancer, bone marrow transplantation can 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 there have been cases of this disease 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.

References

1. Bloom syndrome. (sf). Retrieved on June 23, 2016, from Wikipedia.
2. Bloom Syndrome. (2014). Retrieved on June 23, 2016, from the National Organization for Rare Disorders.
3. Elbendary, A. (December 14, 2015). Bloom Syndrome (Congenital Telangiectatic Erythema). Obtained from Medscape.
4. Ellis, NA, Groden, J., Ye TZ, Straughen, J., Ciocci, S., Lennon, DJ, Proytcheva, M., Alhadeff, B., German, J. (1995). "The Bloom's syndrome gene product is homologous to RecQ helicases." Cell 83: 655-666.
5. German, J., & Sanz, M. &. (sf). 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.
6. Sanz, MG (April 7, 2016). Bloom's Syndrome. Obtained from Gene Reviews.
7. 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.