Bloom-Torre-Machacek syndrome or Bloom syndrome is an extremely rare genetic disorder characterised by short stature and patchy red skin. It is a very rare disorder, with reliable statistics not generally available. However, studies show that occurrence is more common among Jewish people living in Central and Eastern Europe.
People affected with the Bloom syndrome have an increased predisposition to multiple cancers and other diseases like diabetes, often with an onset at an early age. They are born with a low birth weight and length, and are usually skinny in appearance. They later attain a height of less than 5 feet and weigh not more than 50 pounds, on an average.
Skin rashes develop at an early age and aggravate upon exposure to the sun. These rashes with redness are caused by dilation and congestion of blood capillaries, a condition prevalent in Bloom syndrome. Often, the blood capillaries undergo permanent dilation, resulting in red blotches. These blotches spread across the bridge of the nose in a butterfly pattern. Other sun-exposed areas of the skin, such as the back of the neck, hands, etc. are also susceptible to such rashes.
Apart from rashes, people affected by this inherited disorder also show symptoms such as a high-pitched voice, and distinctive features such as a long, narrow face, prominent nose and ears, and a pointed lower jaw.
Other complications like recurrent pneumonia, ear infections and diabetes, arise due to moderate or severe immune deficiency. Most men affected with Bloom syndrome are unable to produce sperm and, hence, are infertile. Women usually experience an early menopause and show reduced infertility.
Mutation in a gene, called the BLM gene, is the major cause for this genetic problem. The BLM gene is an important contributor in the process of cell division. When something goes wrong with the BLM gene, there is abnormal cell division, and the resultant new cells are faulty and unable to perform their intended functions.
Every cell has a set of 23 pairs of chromosomes that carry genetic information, which is contained in the double helix DNA strands in them. When a cell divides, the DNA gets duplicated or copied, so that each new cell gets a complete new set of 23 pairs of chromosomes. During this duplication, the intertwined DNA strands temporarily unwind to enable copying.
This whole process of duplicating is very controlled. Proteins called RecQ helicases, which are present in the DNA, are crucial to this process of unwinding. Helicases help in the upkeep of the structure and integrity of the DNA by controlling the division and, hence, are often referred to as the caretakers of the genome.
The copied DNA are arranged into two identical structures, called sister chromatids. These sister chromatids are attached and exchange DNA during the early stages of cell division.
The BLM gene provides instructions to the RecQ helicases and controls the division. Thus, they help a lot in the maintenance of DNA integrity. The BLM protein stabilises this exchange between chromatids, thus, controlling the whole process of cell division.
When a BLM gene gets mutated, it fails to control the exchange between sister chromatids that continues unabatedly. The exchange accelerates to almost ten-fold, thus, destabilising the DNA. This results in faulty DNA formation with gaps in the structure, which in turn hamper normal cell activity. The presence of abnormal cells and uncontrolled cell duplication is what gives rise to cancer and other disorders characterising this inherited disorder.
The abnormal cell division also results in frequent cell death, which is the reason for stunted growth in individuals affected by this genetic issue.
The inheritance of this genetic disorder is through autosomal recessive pattern. Human beings have 23 pairs of chromosomes, of which 22 are called autosomes. The 23rd pair is the sex-determining chromosome called allosome.
Autosomes can be inherited in either a dominant or recessive manner. Autosomal recessive inheritance means that both parents must be the carriers, in order for a child to be affected. While the inherited disorder does not show up but remains recessive in parents, inspite of being the carrier. One in four of their progeny are most likely to inherit this genetic disorder. Two out of four of their children have a good chance of being further carriers.
The presence of this genetic disorder is confirmed in two ways, either by looking for a four-armed chromatid interchange configuration, also known as quadriradial, or a greatly increased sister chromatid exchange in cells.
Molecular genetic analysis of the BLM gene also reveals the presence of this genetic disorder in an individual.
Treatment of the occurrence of other secondary diseases as a result of this inherited disorder follows the normal routine. For instance, ear infections and pneumonia are treated using routine antibiotics. Diabetes is treated in the usual manner. Cancer treatment is also the same, except that the sensitive state of cells mandates a reduced dosage of chemicals or radiation. The presence of Bloom syndrome also affects the duration of chemo or radio therapy, as hypersensitive cells cannot withstand the harshness for a long time.
Precautionary measures such as periodic check-ups for signs of malignancy, screening for different types of cancers, and avoiding exposure to the sun can be helpful for people suffering from this inherited disorder.
Genetic counselling to individuals belonging to families with known history of this genetic disorder is essential, in order to distinguish between the carriers and non-carriers, and to later take precautionary measures, accordingly.