Bloom syndrome is a rare autosomal recessive genetic disorder characterized by short stature, predisposition to the development of cancer, and genomic instability.
BS is caused by mutations in the BLM gene which is a member of the RecQ DNA helicase family.
Bloom syndrome is an autosomal recessive disorder, caused by mutations in the maternally- and paternally-derived copies of the gene BLM.
BS is a member of a class of clinical entities that are characterized by chromosomal instability, genomic instability, or both and by cancer predisposition.
Bloom syndrome cells exhibit genomic instability that includes excessive crossovers between homologous chromosomes and sister chromatid exchanges.
There is an enormous increase in exchange events between homologous chromosomes or sister chromatids and there are increases in chromosome breakage and rearrangements compared to persons who do not have Bloom’s syndrome.
The BLM protein is important in maintaining the stability of the DNA during the replication process.
Deficiencies in homologous recombination have been strongly linked to cancer formation: each of the cancer-related diseases Bloom syndrome
Lack of BLM protein or protein activity leads to an increase in mutations.
The most prominent feature of the BS is proportional small size.
The small size is apparent in utero, and at birth, neonates exhibit rostral to caudal lengths, head circumferences, and birth weights that are typically below the third percentile.
A facial rash appears most prominently on the cheeks, nose, and around the lips, and is the second most commonly noted feature.
The rash develops early in life as a result of sun exposure.
It is an erythematous, inflamed, and telangiectatic rash, that is characterized by dilated blood vessels at the skin’s surface.
The rash commonly also affects the backs of the hands and neck, and it can develop on any other sun-exposed areas of the skin.
The rash is variably expressed.
The rash is present in a majority but not all persons with Bloom syndrome.
The rash is on average less severe in females than in males.
The sun sensitivity can resolve in adulthood.
Additional dermatologic changes include: hypo-pigmented and hyper-pigmented areas, cafe-au-lait spots, and telangiectasias, which can appear on the face and on the ocular surface.
BS has a characteristic facial appearance that includes a long, narrow face; prominent nose, cheeks, and ears; and micrognathism or undersized jaw.
Patients have is high-pitched and squeaky voice.
Other processes associated with BS: moderate immune deficiency, characterized by deficiency in certain immunoglobulin classes and a generalized proliferative defect of B and T cells.
The immune deficiency is thought to be the cause of recurrent pneumonia and middle ear infections in persons with the syndrome.
Infants can exhibit frequent gastrointestinal upsets, with reflux, vomiting, and diarrhea, and there lack in interest in food.
There are endocrine disturbances, particularly abnormalities of carbohydrate metabolism, insulin resistance and susceptibility to type 2 diabetes, dyslipidemia, and compensated hypothyroidism.
Persons with BS exhibit a paucity of subcutaneous fat, reduced fertility, azoospermia in males and premature premature menopause females.
Despite these reductions, several women with Bloom syndrome have had children, and there is a single report of a male with Bloom syndrome bearing children.
There is no evidence that intellectual disability is more common in Bloom syndrome than in other people.
Its most serious and frequent complication is cancer.
Greater than persons 51.6% have been diagnosed with a malignant neoplasm.
The types of cancer and the anatomic sites at which they develop resemble the cancers that affect persons in the general population, but diagnosis occurs earlier than for the same cancer in normal persons.
Many patients with Bloom syndrome have been diagnosed with multiple cancers.
The average life span with BS is approximately 27 years.
The most common cause of death in BS is from cancer.
Complications of BS include chronic obstructive lung disease and type 2 diabetes.
A closely related entity-Bloom-syndrome-like disorder (BSLD) which is caused by mutations in components of the same protein complex to which the BLM gene product belongs, including TOP3A, which encodes the type I topoisomerase, topoisomerase 3 alpha, RMI1, and RMI2.
The features of BSLD include small size and dermatologic findings, such as cafe-au-lait spots, and the presence of the once pathognomonic elevated SCEs is reported for persons with mutations in TOP3A and RMI1.
Bloom syndrome shares some features with Fanconi anemia possibly due to the overlap in the function of the proteins mutated in this related disorder.
The mutations in BLM gene associated with Bloom syndrome are nulls and missense mutations.
The cells from persons with Bloom syndrome exhibit genomic instability that is characterized by hyper-recombination and hyper-mutation.
Human BLM cells are sensitive to DNA damaging agents such as UV and methyl methanesulfonate, indicating deficient repair capability.
The rate of sister chromatid exchange in Bloom’s syndrome is approximately 10 fold higher than normal and quadriradial figures, which are the cytologic manifestations of crossing-over between homologous chromosome, are highly elevated.
Other chromosome manifestations include chromatid breaks and gaps, telomere associations, and fragmented chromosomes occur.
BLM very likely functions in DNA replication, as cells from persons with Bloom syndrome exhibit multiple defects in DNA replication, and they are sensitive to agents that obstruct DNA replication.
The greatly elevated rate of mutation in Bloom syndrome and the genomic instability is associated with a high risk of cancer.
The cancer predisposition is characterized by a broad spectrum of cancers including leukemias, lymphomas, and carcinomas, early age of onset relative to the same cancer in the general population, and multiplicity, that is, synchronous or metachronous cancers.
Cancer may develop at any age with the BS.
Bloom syndrome is diagnosed by any of three tests:
The presence of quadriradial in cultured blood lymphocytes.
An elevated levels of sister chromatid exchange in cells of any type.
The mutation in the BLM gene.
There is no specific treatment.
Avoiding sun exposure and using sunscreens can help prevent some of the cutaneous changes associated with photo-sensitivity.
The disorder is relatively more common amongst people of Central and Eastern European Ashkenazi Jewish background.
Approximately 1 in 48,000 Ashkenazi Jews are affected by Bloom syndrome, who account for about one-third of affected individuals worldwide.