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Bloom Syndrome (Congenital Telangiectatic Erythema)
Updated: Feb 28, 2007
Introduction
Background
Bloom syndrome is a rare autosomal recessive disorder characterized by telangiectases and photosensitivity, growth deficiency of prenatal onset, variable degrees of immunodeficiency, and increased susceptibility to neoplasms of many sites and types. The New York dermatologist David Bloom first described the syndrome in 1954.
Pathophysiology
The syndrome is caused by a mutation in the gene designated BLM, traced to band 15q26.1. The protein encoded by the normal gene has DNA helicase activity and functions in the maintenance of genomic stability. Increased sister chromatid exchanges and chromosomal instability also occur, which is assumed to be responsible for the phenotype and the cancer predisposition. In 1989, Nicotera et al suggested that the major biochemical defect in persons with Bloom syndrome is chronic overproduction of the superoxide radical anion. They thought that inefficient removal of peroxide might be responsible for the high rates of sister chromatid exchange and chromosomal damage in Bloom syndrome cells.
Frequency
United States
More than 170 case reports have been made. The frequency of parental consanguinity is much greater than in the general population.
International
The disease is more common in Ashkenazi Jews but has been reported in Japan and other countries.
Mortality/Morbidity
Early diagnosis of leukemia is, at present, not known to improve the chances of curative therapy. Frequent hematologic examinations in children is not advised for fear of untoward psychologic effects. Allogeneic marrow grafting has not been performed in Bloom syndrome patients. Men with Bloom syndrome are sterile; women have reduced fertility and a shortened reproductive span. Bloom syndrome patients who become pregnant are at high risk for premature delivery. Intelligence is usually normal, although mild deficiency has occurred in a few affected persons. Diabetes occurs in approximately 10% of individuals with Bloom syndrome.
Race
Bloom syndrome is more common in eastern European Ashkenazi Jews.
Sex
The male-to-female ratio is 1.3:1.
Age
This condition occurs in the first few months of life.
Clinical
History
- Physical features
- Growth delay is the most impressive clinical feature of Bloom syndrome and is usually the first manifestation that causes the parents to seek medical attention.
- Other associated physical features and immunodeficiency are not present or recognizable at birth.
- The growth deficiency has a prenatal onset, apparent from term birth measurements, and persists throughout life.
- More than half the children are significantly underdeveloped in physical stature until age 8 years.
- Neoplasia
- Patients with Bloom syndrome have an overall 150- to 300-times increased risk of malignancy compared with the general population.
- Twenty percent of patients with Bloom syndrome develop malignancies (eg, acute leukemia, lymphoma, gastrointestinal adenocarcinoma).
- Immunology: Patients with Bloom syndrome have decreased immunoglobulin A and immunoglobulin M, with recurrent respiratory and gastrointestinal tract infections.
Physical
- Skin
- Telangiectatic erythema appears as macules or plaques in a butterfly distribution on the face and other photodistributed areas. Eyes may have scleral telangiectases.
- Cheilitis with crusting or bleeding is present.
- Café au lait macules with adjacent hypopigmented areas appear as twin spotting.
- Craniofacial/body habitus
- Lack of subcutaneous fat contributes to a characteristic birdlike facies with a long, narrow face and prominent nose. The skull shape is dolichocephalic.
- Patients have malar hypoplasia and small mandibles.
- Affected individuals have relatively large protruding ears.
- Long limbs, disproportionally large hands and feet, and progressive contracture of hands and feet are noted. Upper extremities are long in proportion to body length.
- Quick, birdlike movements are characteristic.
- Patients have short stature.
- Ear, nose, and throat: Patients have a high-pitched voice.
- Endocrine: Patients have primary hypogonadism.
Causes
The condition is genetic with an autosomal recessive pattern of inheritance. The gene locus is band 15q26.1.
- Cytogenetic findings in a Bloom syndrome patient with acute myeloid leukemia of the French-American-British subtype M1 showed preferential occurrence of total or partial loss of chromosome 7.
- Mutation of the DNA ligase I gene may account for the primary metabolic defect in Bloom syndrome, not due to a reduction in the number of protein molecules or to inhibitory substances, but rather to the ATP-binding and hydrolytic activity of the enzyme. DNA ligase I and DNA polymerase alpha are enzymes that function during DNA replication; DNA ligase II and DNA polymerase-beta function during DNA repair.
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References
Bloom D. Congenital telangiectatic erythema resembling lupus erythematosus in dwarfs; probably a syndrome entity. AMA Am J Dis Child. Dec 1954;88(6):754-8. [Medline].
Cheok CF, Bachrati CZ, Chan KL, et al. Roles of the Bloom's syndrome helicase in the maintenance of genome stability. Biochem Soc Trans. Dec 2005;33(Pt 6):1456-9. [Medline].
Chisholm CA, Bray MJ, Karns LB. Successful pregnancy in a woman with Bloom syndrome. Am J Med Genet. Aug 1 2001;102(2):136-8. [Medline].
Ellis NA, German J. Molecular genetics of Bloom''s syndrome. Hum Mol Genet. 1996;5 Spec No:1457-63. [Medline].
German J. Bloom syndrome: a mendelian prototype of somatic mutational disease. Medicine (Baltimore). Nov 1993;72(6):393-406. [Medline].
German J. Bloom syndrome X. The cancer proneness points to chromosome mutation as a crucial event in human neoplasia. In: German J, ed. Chromosome Mutation and Neoplasia. New York, NY: Alan R. Liss; 1983:. 347-57.
German J. Bloom''s syndrome. XX. The first 100 cancers. Cancer Genet Cytogenet. Jan 1997;93(1):100-6. [Medline].
German J. Bloom''s syndrome. Dermatol Clin. Jan 1995;13(1):7-18. [Medline].
Gretzula JC, Hevia O, Weber PJ. Bloom''s syndrome. J Am Acad Dermatol. Sep 1987;17(3):479-88. [Medline].
Keller C, Keller KR, Shew SB, Plon SE. Growth deficiency and malnutrition in Bloom syndrome. J Pediatr. Apr 1999;134(4):472-9. [Medline].
Kim YM, Yang I, Lee J, Koo HS. Deficiency of Bloom's syndrome protein causes hypersensitivity of C. elegans to ionizing radiation but not to UV radiation, and induces p53-dependent physiological apoptosis. Mol Cells. Oct 31 2005;20(2):228-34. [Medline].
Krejci L, Van Komen S, Li Y, et al. DNA helicase Srs2 disrupts the Rad51 presynaptic filament. Nature. May 15 2003;423(6937):305-9. [Medline].
Magnusson KP, Sandstrom M, Stahlberg M, et al. p53 splice acceptor site mutation and increased HsRAD51 protein expression in Bloom''s syndrome GM1492 fibroblasts. Gene. Apr 4 2000;246(1-2):247-54. [Medline].
Seki M, Nakagawa T, Seki T, et al. Bloom helicase and DNA topoisomerase IIIalpha are involved in the dissolution of sister chromatids. Mol Cell Biol. Aug 2006;26(16):6299-307. [Medline].
Straughen J, Ciocci S, Ye TZ, et al. Physical mapping of the bloom syndrome region by the identification of YAC and P1 clones from human chromosome 15 band q26.1. Genomics. Jul 1 1996;35(1):118-28. [Medline].
Wu L, Davies SL, North PS, et al. The Bloom''s syndrome gene product interacts with topoisomerase III. J Biol Chem. Mar 31 2000;275(13):9636-44. [Medline].
Further Reading
Keywords
BS, congenital telangiectatic erythema, Bloom's syndrome, telangiectases, photosensitivity, grow deficiency, growth retardation, growth restriction, malignancy predisposition
