Bloom syndrome is a very rare autosomal recessive genetic disease that stems from mutations in genes responsible for DNA repair. Predisposition to various malignancies (mainly of the hematopoietic system, the gastrointestinal tract, the skin, and the genitourinary tract), photosensitivity, frequent infections of the lungs and ear, growth deficiency, sterility, and learning disabilities are some of the most common findings in this patient population. The diagnosis rests on clinical criteria and molecular genetic studies that confirm mutations responsible for this syndrome.
The clinical presentation of patients suffering from Bloom syndrome encompasses a myriad of signs and symptoms      :
Other important signs and symptoms of Bloom syndrome are variable intellectual disability, feeding problems (often due to gastroesophageal reflux disease), immunosuppression that predisposes to infection (lungs, skin, and ears are main sites), retinopathies, glucose intolerance, and a very frequent occurrence of one or more malignant diseases - lymphomas and gastrointestinal neoplasias being the most common     .
Because of numerous complications and associated conditions that occur, up to one-third of patients die in their third decade of life . For this reason, an early diagnosis is critical. The physician must obtain a detailed patient history that will focus on the onset of symptoms and their progression. A heterogeneous anamnesis (particularly from the parents) might be useful in the case of younger children and adolescents. In addition to a complete family history (which must be covered due to the autosomal recessive pattern of inheritance), Ashkenazi Jew ancestry carries a very high risk for the development of Bloom syndrome (carrier state is estimated in approximately 1 in 100 individuals), meaning that demographic factors should also be thought of when establishing the cause  . An early onset of chronic obstructive pulmonary disease (COPD) and diabetes mellitus is an additional clue that points toward this diagnosis . If solid evidence toward Bloom syndrome is obtained during history taking and physical examination (which is essential for establishing the main clinical findings), a definitive diagnosis can be pursued through genetic testing. Identification of mutations in the BLM gene that codes for the RecQL3 helicase enzyme (a very important enzyme involved in DNA repair) confirm the diagnosis  .
Treatment is targeted at the various manifestations of the disease. Supplementation with growth hormone has proven ineffective in resolving growth abnormalities. Feeding through intubation can help in increasing fat deposition but has no effects on growth. Because many chemotherapeutic agents are directed at mechanisms involved in cell replication and differentiation, it is often necessary to reduce both the dose and duration of cancer treatment. The absence of specific information about dosage and duration of the treatment in those patients is particularly challenging for the physician. Diabetes mellitus in patients with Bloom is not treated in a different manner than that occurring in the normal population. Finally, psychosocial intervention is very important. Family and teachers are advised to behave with the patients according to their true age rather than what is suggested by their stature.
Patients with Bloom syndrome have 150 to 300 times the risk of developing malignancies in comparison to normal individuals. Malignancies will occur in around 20% of patients, particularly leukemias that usually manifest around a mean age of 22 years. Patients who survive beyond 22 years will develop solid tumors at an average of 35 years. Around 10% of patients are affected by diabetes mellitus across their life time, although the risk of infection and the sensitivity to sunlight decreases with age.
Bloom syndrome is transmitted in an autosomal recessive fashion, so that each parent of the individual affected carries one copy of the gene with the mutation without showing any symptoms. The gene involved is the BLM gene, resulting in a defective BLM protein. This protein plays a critical role in several domains. A mutation increases chromosomal exchange, in particular between sister chromatids and paternal and maternal chromosomes. In addition, BLM abnormalities impair the repair of DNA damage caused as a result of exposure to ultraviolet light, manifesting in increased sensitivity to sunlight. Mutations accumulate in the genome and ultimately increase the risk of cancer in patients suffering from this disorder.
The major end protein affected in Bloom syndrome is DNA ligase I, an enzyme involved in DNA replication. Scientists were able to show that patients with Bloom syndrome have a DNA ligase I with different physical properties, particularly in regards to heat sensitivity and the ability to aggregate  . Other studies further corroborated the connection between Bloom syndrome, DNA Ligase I and metabolic abnormalities associated with the disease, in addition to uncovering the specific pathophysiological mechanisms involved. They report changes in the hydrolytic capacity of DNA Ligase I and its ability to bind ATP, without any reduction of the level of expression of the protein or other inhibitory molecules . DNA Ligase I is part of a broader complex of enzymes involved in DNA repair and replication, that also includes DNA polymerase alpha, DNA polymerase beta and DNA ligase II.
Bloom syndrome is a rare disease and affects men slightly more than women. Reports in the literature are scarce because only few hundred cases have been recorded, but the available reports indicate a higher incidence of disease in families with consanguinity among parents, as compared to the general population. As revealed through records of Bloom patients' registry, the syndrome has a high carrier frequency in the ratio of 1:120 and accounts for 25 % patients among Ashkenazi Jews . The syndrome has also been reported from Japan and other countries in families where there is consanguinity among parents. In comparison to the general population, patients also have 150 to 300 times higher risk of developing malignancy in their life time . It is associated with premature delivery in affected pregnant women and diabetes in approximately 10% of patients. It manifests in the first months of life but does not seem to decrease overall intelligence levels, except in select cases.
Bloom syndrome, also known as telangiectacic erythema, results from a mutation to the BLM gene present on chromosome 15. The exact location can be traced to 15q26.1   . The BLM protein is a member of the RecQ family of helicases and is composed of 1417 amino acids. It is usually present in the nuclear matrix and is essential for DNA repair and replication. Mutations in the BML gene lead to defective protein that result in loss of genomic stability in somatic cells, and thus significantly increasing the risk of malignancy .
Around 60 mutations of the BLM gene have been associated with Bloom syndrome. Among the most common of mutations, which is present mostly among Ashkenazi Jews, involves a substitution of 6 nucleotides with 7 new ones at position 2281 in the gene sequence. Reports indicate an increased rate of chromatic exchange, chromosomal gaps, breaks and structural rearrangement and is 10 times more elevated in comparison to the normal population   .
Bloom syndrome has been associated with Fanconi anemia, given the involvement of proteins MM1 and MM2 in both diseases. They tend to show similar phenotypes and share distinctive features such as abnormalities in skeletal growth and short stature, failure of the bone marrow and hematologic cancers. Although the two diseases are not related genetically, pathophysiological mechanisms include disturbances along common pathways in DNA repair, involving the complexes , BRAFT and FANCM  .
Patients with Bloom syndrome are known to be sensitive to sunlight with a reduction of the threshold for minimal erythema for both, UV-A and UV-B light . This is caused by an increased vulnerability of the DNA to ultraviolet radiation, particularly for wavelengths corresponding to 313 nm. They are especially susceptible to radiation in UV-A range although it is important to note that, unlike in xeroerma pigmentosa, there is increased phototoxicity and not photocarcinogenicity .
Other prominent features of the disease are related to the immune system and affect both the humoral and cellular immune responses . They include deficits in lymphocytic proliferation, abnormal immunoglobulin synthesis and impaired reaction to mitogen stimulation.
There is no cure for Bloom syndrome but important preventive measures can be performed to reduce the risk of complications. Sunscreens and the avoidance of sunlight may prevent the skin damage associated with sun exposure. In addition, patients are recommended to avoid known mutagens . Immunoglobulin replacement can help in preventing infections due to deficiencies in immunoglobulin production. In addition, patients should be periodically screened for any malignancy .
David Bloom was the first to describe Bloom syndrome in 1954 in a group of patients suffering from facial erythema and short stature . The disease is most commonly encountered among Ashkenazi Jews (Jews of Central and Eastern European origin) and is chiefly characterized by growth abnormalities and sun sensitivity usually manifested by erythema of the face upon sun exposure. The facial rash has a butterfly shape over the cheeks and the nose and can also involve other areas of the body subjected to sunlight, including the forearms and the back of hands.
Individuals with Bloom syndrome also suffer from a range of other abnormalities. They commonly develop frequent infections of the lung and the middle ear, most likely due to a higher incidence of gastroesophageal reflux associated with aspiration. As the age advances, the patient is more likely to have chronic obstructive pulmonary disease with severe bronchiectasis, as well as diabetes mellitus resembling the disease in the normal population. They are at a significantly increased risk of acquiring various malignancies that can affect different tissues at different sites of the body, necessitating frequent screening and monitoring. In addition, the disease affects the reproductive system with women undergoing early menopause although retaining their ability to conceive and men unable to produce sperm, leading to infertility.
Bloom syndrome was first described in 1954 by dermatologist David Bloom. It is a rare genetic disease, chiefly characterized by growth abnormalities and short stature. Patients usually retain normal body proportions although the head is disproportionately smaller. Increased sensitivity to sunlight, resulting especially in cracking and blistering of the lower lip, is another prominent feature and can be prevented with adequate avoidance of sun exposure. Growth abnormalities are commonly noticed at birth and infants typically show problems with feeding and decreased interest in nursing and eating. Patients develop frequent infections, especially of the lung (pneumonia) and the middle ear (otitis media), possibly resulting from the increased risk of aspiration and gastroesophageal reflux.
Bloom syndrome additionally affects the development of reproductive system. While women undergo premature menopause, they retain their ability to conceive. But, men are faced with an inability to develop normal sperm (azoospermia), leading to infertility. Patients with Bloom syndrome have a higher risk of developing several specific disorders as they age. These include chronic obstructive disease, mild diabetes mellitus that closely resembles the disease observed in the normal population as well as a variety of cancers that can affect different tissue types in various locations. The risk of developing malignancy makes it particularly important for patients to undergo regular screening and monitoring for the early detection of any cancer and the prevention of resulting complications. Patients with Bloom syndrome appear to have a normal mental capacity but demonstrate a decreased interest in learning, with a select few being affected by mental retardation.