What is Bloom Syndrome (Bloom-Torre-Machacek Syndrome or Congenital Telangiectatic Erythema)?
Bloom syndrome, also known as Bloom-Torre-Machacek syndrome or congenital telangiectatic erythema, is a rare genetic skin condition known for causing an unstable genetic makeup and increased risk for various types of cancer. This condition is caused by mutations or changes in a gene called BLM. This mutation causes the production of an irregular DNA protein, which handles the arrangement and replication of our genetic material.
A unique feature, diagnostic for this syndrome, is unusually high exchanges between sister chromatids (pairs of identical DNA molecules) and quadriradial configurations (special four-armed chromosome structures). Key symptoms of Bloom syndrome include stunted growth from before birth, mild weakness in the immune system, high sensitivity to sun leading to lupus-like facial skin lesions (skin damage resembling a chronic skin disorder), type 2 diabetes, and hypogonadism (underactivity of the gonads – testes in men, ovaries in women).
Unfortunately, the increased risk of cancer in people with Bloom syndrome can lead to a shortened life span and higher illness rates. Hence, proper understanding and medical attention towards this condition are necessary.
What Causes Bloom Syndrome (Bloom-Torre-Machacek Syndrome or Congenital Telangiectatic Erythema)?
Bloom syndrome is a rare genetic disorder that leads to problems with the stability of chromosomes, the parts of our cells that carry our genes. This syndrome occurs due to changes in a gene known as BLM, found in a specific area of chromosome 15. This BLM gene creates a protein that interacts with two other proteins, DNA topoisomerase IIIα and RMI, to help keep our DNA stable.
When the BLM gene has mutations or errors in it, the process of copying DNA becomes flawed, leading to more frequent changes and breaks in chromosomes. This increased ‘genomic instability’ – when there’s a lot of change in the genetic material of the cells – means that people with Bloom syndrome may be at a higher risk of developing cancer.
Risk Factors and Frequency for Bloom Syndrome (Bloom-Torre-Machacek Syndrome or Congenital Telangiectatic Erythema)
Bloom syndrome is a rare disorder, with only 281 known cases recorded in the Bloom Syndrome Registry as of 2018. It’s mostly found in the Ashkenazi Jewish population, who make up 25% of the affected individuals worldwide. In fact, about 1% of Ashkenazi Jews carry the gene mutation that causes Bloom Syndrome. It is slightly more common in males.
- There are only 281 people registered with Bloom Syndrome as of 2018.
- The Ashkenazi Jewish population is the most commonly affected group.
- Approximately 1% of Ashkenazi Jews are carriers of the gene mutation that causes Bloom Syndrome.
- About 170 cases have been reported in the United States.
- It’s slightly more common in males.
Signs and Symptoms of Bloom Syndrome (Bloom-Torre-Machacek Syndrome or Congenital Telangiectatic Erythema)
Bloom Syndrome is a medical condition that causes severe growth issues before and after birth, commonly noticeable through a small head size and distinct facial features such as a particular nose shape, hollow cheeks, and protruding ears. Babies with Bloom Syndrome often have a high-pitched voice and might lack some of their upper lateral teeth. Parents usually notice their child’s small size compared to other children their age, but this can lead to confusion with dwarfism.
People with Bloom Syndrome have skin that’s very sensitive to sunlight, often causing a rash similar to lupus on their faces. Other skin conditions such as UV-triggered lesions might also occur in other areas exposed to the sun, like the back of the hands or the forearms. Telangiectasias and poikiloderma, which are small clusters of dilated blood vessels, might appear on the skin and eyes’ sclera during the early years of life due to sun exposure. Other skin findings can include mouth fissures, differently coloured spots, and unusual patchy areas of light and dark skin.
Bloom Syndrome can also lead to other issues such as underdeveloped sexual organs, intellectual disability, late onset of type 2 diabetes, and cause the immune system to weaken, leading to frequent ear and sinus infections during infancy. Sometimes, levels of certain types of antibodies (IgA, IgM, IgG) are lower than normal. Vomiting, diarrhea, and gastroesophageal reflux can cause severe dehydration in infancy, which might further lead to aspiration from reflux disease, contributing to more frequent cases of pneumonia and chronic lung disease. Lung failure is the second most common cause of death in this population.
People suffering from Bloom Syndrome have a higher risk of developing various types of cancer, with up to 50% diagnosed with cancer at some point in their life. They usually develop tumors earlier than the general population and can have multiple independent primary cancers of various types and in different parts of the body. The mean age for a cancer diagnosis is 23 years, and death typically occurs before age 30. Leukemias and non-Hodgkin lymphomas are frequent in the first two decades of life. These patients can also develop other types of cancers, with colorectal cancer being the most common. Death due to complications from cancer is the most common for these patients.
Testing for Bloom Syndrome (Bloom-Torre-Machacek Syndrome or Congenital Telangiectatic Erythema)
If doctors suspect Bloom syndrome based on signs and symptoms you’re experiencing, they will typically confirm the diagnosis using a specific type of genetic test. This test looks for increases in something called sister chromatid exchanges or quadriradial configurations in certain types of cells, like lymphocytes or fibroblasts. These specific changes are markers for Bloom syndrome. In some cases, detailed mutation analysis is also done.
Doctors also recommend carrying out genetic and prenatal testing for people who are at a high risk of carrying the condition, to prepare for any potential risks and ensure the best possible care.
The doctor will also run some blood tests. This includes a complete blood count that checks for different type of cells in your blood. In people with Bloom syndrome, the lymphocytes, a type of white blood cell, tend to be low but within the normal range. These patients usually also have a higher number of a specific type of T cell (a part of the immune system), but fewer memory B cells (another type of immune cell).
In addition, there may be shortages in the body’s levels of certain immune system proteins called IgM, IgA, and possibly IgG. These proteins, also known as antibodies, play critical roles in defending the body against infections. So, lower levels of these proteins can make a person more prone to infections.
Treatment Options for Bloom Syndrome (Bloom-Torre-Machacek Syndrome or Congenital Telangiectatic Erythema)
Dealing with rare and complex health conditions often requires a mix of many skills and strategies. One such complex condition doesn’t have a universally agreed-upon treatment yet due to its uniqueness and the challenges associated with it. From the time of birth, special attention is given to maintaining fluid balance in the body to avoid severe dehydration, which can be life-threatening. Also, using feeding tubes can be helpful in preventing dehydration and undernourishment. However, feeding tubes don’t seem to help increase height or the pace of growth.
Using growth hormones has been tested, but they don’t seem to speed up growth or boost adult height. In fact, the use of growth hormones could potentially increase the risk of developing tumors. The use of appropriate antibiotics is pursued for treating infections. Some patients who have significant issues with immunity might need to be given immune globulins (proteins in the immune system that fight off bacteria and viruses) through an intravenous (IV) line. Continuous monitoring and management by an endocrinologist (doctor specializing in hormonal disorders) is crucial for treating diabetes.
For skin protection, regular skin checks are suggested along with avoiding direct sun exposure. There’s a debate about whether to do screenings for blood-related cancers in kids, as early detection hasn’t shown any clear benefits to forecasting outcomes. However, adults do benefit from early detection and surgical treatment of some types of cancer, specifically in the breast, cervix, and colon. Therefore, yearly screenings for these cancers are advised.
Given the increased risk of damage to chromosomes, it’s suggested that patients reduce their exposure to radiation. Instead of using CT scans or X-rays, MRI and ultrasound scans are more advisable for cancer screenings and diagnoses. Due to the potential for increased toxicity, the doses of chemotherapy drugs may need to be adjusted. One drug in particular, 5-fluorouracil, is known to cause high levels of DNA fragmentation, and thus its use needs careful monitoring. Radiotherapy, which uses high-energy rays to destroy cancer cells, is discouraged. Proton beam therapy, a type of radiotherapy that uses protons rather than x-rays, has been found as a safer alternative.
What else can Bloom Syndrome (Bloom-Torre-Machacek Syndrome or Congenital Telangiectatic Erythema) be?
When a doctor is trying to diagnose a patient, they must consider various possibilities based on the symptoms the patient presents with. Here are some potential diagnoses they could consider:
For patients with a short stature but normal body proportions, possibilities could be:
- Skeletal dysplasia
- Growth hormone deficiency
- Constitutional delay
If the patient is showing signs of a genetic disorder that makes them sensitive to sunlight, the doctor might consider:
- Xeroderma pigmentosa
- Cockayne syndrome
- Rothmund-Thomson syndrome
- Smith-Lemli-Opitz syndrome
Finally, if the patient has symptoms indicating a disorder related to chromosome breakage, potential diagnoses could be:
- Nijmegen breakage syndrome
- DNA ligase IV deficiency
- Cernunnos deficiency
What to expect with Bloom Syndrome (Bloom-Torre-Machacek Syndrome or Congenital Telangiectatic Erythema)
Many people with Bloom syndrome live into adulthood. On average, the age at which people with this condition pass away is 26 years old. This is typically due to complications related to cancer. The second most frequent cause of death in people with Bloom syndrome is chronic lung disease.
Possible Complications When Diagnosed with Bloom Syndrome (Bloom-Torre-Machacek Syndrome or Congenital Telangiectatic Erythema)
Patients undergoing chemotherapy and radiation often experience severe side effects like extreme reduction in the activity of the bone marrow, even when given in lower doses. This makes treating malignancies quite challenging. However, there have been instances of successful treatment with proton beam therapy. Despite this, even those who have beaten cancer can, unfortunately, face life-threatening complications from pneumonia, chronic lung disease, liver disease, or severe body-wide infections, like sepsis.
Common Complications:
- Extreme reduction in bone marrow activity
- Difficulty in treating malignancies or cancer
- Need for intensive treatments like proton beam therapy
- Risks of pneumonia
- Risks of chronic lung disease
- Risks of liver disease
- Risks of body-wide infections like sepsis, even after remission
Preventing Bloom Syndrome (Bloom-Torre-Machacek Syndrome or Congenital Telangiectatic Erythema)
Patients and their families should be informed about the serious risk of developing cancer and the generally unfavorable outcomes associated with this condition. It’s also important to provide guidance related to genetics. This helps patients understand the role that genes may play in the development of this condition.
