Bloom syndrome

Abstract

Bloom Syndrome (BS, MIM #210900) is an autosomal recessive genetic disorder caused by a mutation in the BLM gene, which codes for the DNA repair enzyme RecQL3 helicase. Without proper DNA repair mechanisms, abnormal DNA exchange takes place between sister chromatids and results in genetic instability that may lead to cancer, especially lymphoma and acute myelogenous leukemia, lower and upper gastrointestinal tract neoplasias, cutaneous tumors, and neoplasias in the genitalia and urinary tract. BS patients are usually of Ashkenazi Jewish descent and exhibit narrow facial features, elongated limbs, and several dermatologic complications including photosensitivity, poikiloderma, and telangiectatic erythema. The most concerning manifestation of BS is multiple malignancies, which require frequent screenings and strict vigilance by the physician. Therefore, distinguishing between BS and other dermatologic syndromes of similar presentation such as Rothmund-Thomson Syndrome, Erythropoietic Protoporphyria, and Cockayne Syndrome is paramount to disease management and to prolonging life. BS can be diagnosed through a variety of DNA sequencing methods, and genetic testing is available for high-risk populations. This review consolidates several sources on BS sequelae and aims to suggest the importance of differentiating BS from other dermatologic conditions. This paper also elucidates the recently discovered BRAFT and FANCM protein complexes that link BS and Fanconi anemia.

Bloom's Syndrome: Clinical Spectrum, Molecular Pathogenesis, and Cancer Predisposition

“…1 ). The rash is characterized primarily by telangiectasia but may also have the characteristics of poikiloderma [Arora et al, 2014]. Over time, the rash often appears on the dorsum of hands and forearms in children and adults.…”

First Two Cases of Bloom Syndrome in Russia: Lack of Skin Manifestations in a BLM c.1642C>T (p.Q548X) Homozygote as a Likely Cause of Underdiagnosis

“…Less than 300 BS patients have been described up to now, with about a quarter of them carrying the biallelic Ashkenazi Jewish founder mutation BLM c.2207-2212delATCTGAinsTAGATTC ( BLM Ash ). Approximately 1% of Ashkenazi Jews are heterozygous for the BLM Ash allele; therefore, the appropriate genetic screening of this population is warranted (see the Bloom Syndrome Registry; http://weill.cornell.edu/bsr/) [Roa et al, 1999;German et al, 2007;Arora et al, 2014;Cunniff et al, 2017].…”

“…If we assume that the total number of Slavs in the world is close to 300 million people, with almost a half of them residing in Russia, one would expect that up to 300-2,700 people of Slavic origin may currently suffer from BS. Perhaps, the actual number of prevalent BS cases in Slavic countries is somewhat lower, given a shortened life expectancy in BS patients [German et al, 2007;Arora et al, 2014;Cunniff et al, 2017]. However, it is still appropriate to expect an increased occurrence of BS in this part of the world.…”

“…The diagnosis of BS may be complicated in some circumstances, given that the only relatively constant features of BS are a short stature and a sun-induced erythema, while the appearance of other disease characteristics may vary [German et al, 2007]. Furthermore, the majority of BS patients described in the literature are carriers of the BLM Ash allele [German et al, 2007;Arora et al, 2014;Cunniff et al, 2017]. It remains to be investigated whether the location of the inactivating mutation within the BLM gene influences the disease phenotype.…”

Phenotypes and genotypes of the chromosomal instability syndromes

“…Increased risk of cancers to 5-8 folds in earlier life, commonly seen myelodysplasia, leukemia, lymphoma, adenocarcinoma and other types of cancers in epithelial tissues is the characteristics of BYyn as well (16). Cytogenetics findings are the aberrant chromosomal rearrangements including quadriradial, chromatid gaps and breaks, increased frequency of sister chromatid exchange (SCE) from the cultured lymphocytes (17).…”