Bloom syndrome

Bloom syndrome is an inherited disorder characterized by short stature, sun-sensitive skin changes, an increased risk of cancer, and other health problems.

People with Bloom syndrome have low birth weight and length. They remain much shorter and thinner than others in their family, growing to an adult height of less than 5 feet.

Affected individuals usually develop dilated blood vessels and reddening in the skin, particularly in response to sun exposure. These changes typically appear as a butterfly-shaped patch of reddened skin across the nose and cheeks. The skin changes may also affect the hands and arms.

People with Bloom syndrome have an increased risk of cancer. They can develop any of the cancers found in the general population, but the cancers arise unusually early in life, and affected individuals often develop more than one type of cancer.

Individuals with this disorder often have a high-pitched voice and distinctive facial features including a long, narrow face; a small lower jaw; a large nose; and prominent ears. Other features affecting some people with Bloom syndrome include learning disabilities, an increased risk of diabetes, chronic obstructive pulmonary disease (COPD), and recurrent infections of the upper respiratory tract, ears, and lungs during infancy. Men with Bloom syndrome usually do not produce sperm, and as a result are unable to father children (infertile). Women with the disorder generally have reduced fertility and experience menopause earlier than usual.

Bloom syndrome is a very rare disorder in most populations, and its overall frequency is unknown. The disorder is more common in people of Central and Eastern European (Ashkenazi) Jewish background, among whom about 1 in 50,000 are affected. Approximately one-third of people with Bloom syndrome are of Ashkenazi Jewish descent.

Mutations in the BLM gene cause Bloom syndrome. The BLM gene provides instructions for making a member of a protein family called RecQ helicases. Helicases are enzymes that bind to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division, and for repairing damaged DNA. Because RecQ helicases maintain the structure and integrity of DNA, they are known as the "caretakers of the genome."

When a cell prepares to divide to form two cells, the DNA that makes up the chromosomes is copied so that each new cell will get a complete set of chromosomes. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. Sister chromatids exchange small sections of DNA (sister chromatid exchange) during this time.

The BLM protein interacts with several other proteins involved in the maintenance of genome integrity. With the help of its partner proteins, BLM suppresses sister chromatid exchanges and helps to maintain DNA stability during the copying process.

BLM gene mutations prevent the BLM protein from performing its function in maintaining genomic stability. As a result of the altered BLM protein activity, the frequency of sister chromatid exchange increases about 10-fold, which is a hallmark of Bloom syndrome. Increased sister chromatid exchange is an indicator of chromosome instability. It is associated with gaps and breaks in the genetic material that impair normal cell activities and cause the health problems associated with this condition. Cancer results from genetic changes that allow cells to divide in an uncontrolled way. Altered BLM protein activity may also lead to an increase in cell death, resulting in slow growth in affected individuals.

Read more about the BLM gene.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.