Bloom ’ s syndrome

Key-words Disease name/synonyms Definition Differential diagnosis Etiology Clinical description Diagnostic methods Epidemiology Genetic counseling Antenatal diagnosis Management including treatment Unresolved questions References Abstract Bloom’s syndrome (BS) is a rare human autosomal recessive disorder belonging to a group of “chromosomal breakage syndromes”. BS is characterized by marked genetic instability, including a high level of sister chromatid exchanges, associated with a greatly increased predisposition to a wide range of cancers commonly affecting the general population. The constant clinical features of BS are proportionate preand postnatal growth retardation and cancer predisposition. Additional clinical features include dolichocephaly, facial sun-sensitive telangiectatic erythema, patchy areas of hyperand hypopigmentation of the skin and moderate to severe immunodeficiency manifested by recurrent respiratory tract and gastrointestinal infections. A 10-fold increase in the rate of sister chromatid exchanges (SCEs) in BS cells compared to normal cells is the only objective criteria for BS diagnosis. Clinical diagnosis is confirmed cytogenetically by demonstrating characteristic chromosome instability. BS arises through mutations in both copies of the BLM gene which encodes a 3’-5’ DNA helicase, a member of the RecQ family. The function of the BLM protein remains unclear, but several lines of evidence support a major role in maintaining genomic stability during DNA replication, recombination and repair. BS frequency in the general population is unknown, probably because this disease is very rare. In Askenazic Jewish population, the frequency of BS is approximately 1 in 48 000. This is due to a founder effect, approximately 1% of the Ashkenasi Jewish population being heterozygous carriers for the blmAsh mutation. There is no curative treatment for BS. However, a physician should carefully follow BS patients in order to ensure early diagnosis of cancer.Bloom’s syndrome (BS) is a rare human autosomal recessive disorder belonging to a group of “chromosomal breakage syndromes”. BS is characterized by marked genetic instability, including a high level of sister chromatid exchanges, associated with a greatly increased predisposition to a wide range of cancers commonly affecting the general population. The constant clinical features of BS are proportionate preand postnatal growth retardation and cancer predisposition. Additional clinical features include dolichocephaly, facial sun-sensitive telangiectatic erythema, patchy areas of hyperand hypopigmentation of the skin and moderate to severe immunodeficiency manifested by recurrent respiratory tract and gastrointestinal infections. A 10-fold increase in the rate of sister chromatid exchanges (SCEs) in BS cells compared to normal cells is the only objective criteria for BS diagnosis. Clinical diagnosis is confirmed cytogenetically by demonstrating characteristic chromosome instability. BS arises through mutations in both copies of the BLM gene which encodes a 3’-5’ DNA helicase, a member of the RecQ family. The function of the BLM protein remains unclear, but several lines of evidence support a major role in maintaining genomic stability during DNA replication, recombination and repair. BS frequency in the general population is unknown, probably because this disease is very rare. In Askenazic Jewish population, the frequency of BS is approximately 1 in 48 000. This is due to a founder effect, approximately 1% of the Ashkenasi Jewish population being heterozygous carriers for the blmAsh mutation. There is no curative treatment for BS. However, a physician should carefully follow BS patients in order to ensure early diagnosis of cancer. Key-words Bloom’s syndrome, cancer predisposition, genetic instability, sister chromatid exchanges, RecQ helicase. Amor-Guéret M. Bloom’s syndrome. Orphanet Encyclopedia. February 2004. http://www.orpha.net/data/patho/GB/uk-Bloomsyndrome.pdf 1 Disease name/synonyms Bloom syndrome (Bloom’s syndrome) Synonyms: Bloom-Torre-Mackacek syndrome, Congenital Telangiectatic Erythema. Definition Bloom’s syndrome (BS) is a rare human autosomal recessive disorder characterized by marked genetic instability associated with a greatly increased predisposition to a wide range of cancers commonly affecting the general population. The predominant and constant clinical feature of BS is proportionate preand postnatal growth retardation. Additional clinical features are dolichocephaly, narrow facies with nasal prominence and malar and mandibular hypoplasia, facial sun-sensitive telangiectatic erythema in the butterfly area, patchy areas of hyperand hypopigmentation of the skin (caféau-lait spots), and moderate to severe immunodeficiency manifested by recurrent respiratory tract and gastrointestinal infections (German, 1993). BS was first described in 1954 as “congenital telangiectatic erythema resembling lupus erythematosus in dwarfs”