AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

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

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Cockayne syndrome is differentiated by the presence of premature aging, deafness, mental retardation, and retinal degeneration.
Rothmund-Thomson syndrome is differentiated by the early onset of poikiloderma and cataracts.
Lupus erythematosus is differentiated by accompanying rheumatologic and serologic associations.
Erythropoietic protoporphyria is differentiated by the presence of red blood cell protoporphyrins and positive red blood cell fluorescence.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• The diagnosis of Bloom syndrome can be confirmed or excluded by a laboratory test known as a chromosome study; blood and skin cells show a characteristic pattern of chromosome breakage and rearrangement. Testing for chromosome instability, including the presence of quadriradicals and increased sister chromatid exchanges, is performed at the US National Institutes of Health and US Armed Forces Institute of Pathology laboratories.
• Immunoglobulin levels should be checked; decreased immunoglobulin A and immunoglobulin M, with or without immunoglobulin G changes, are expected.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

Bloom syndrome has no specific treatment; however, avoiding sun exposure and using sunscreens can help prevent some of the cutaneous changes associated with photosensitivity. Efforts to minimize exposure to other known environmental mutagens are also advisable.

Surgical Care

Surgical oncology care can be instituted as needed for the diagnosis and treatment of malignancies.

Consultations

• Dermatologist for establishing the diagnosis, patient and family education, and sun protection guidance
• Pediatric infectious disease specialist for appropriate treatment of gastrointestinal and respiratory tract infections
• Oncologist for cancer surveillance
• Endocrinologist for short stature and hypogonadism management

Activity

• Men with Bloom syndrome are sterile; women have reduced fertility and a shortened reproductive span. A 19-year-old woman with Bloom syndrome was reported with a successful pregnancy. Preterm labor occurred at 32 weeks' gestation, and the infant was ultimately delivered at 35 weeks' gestation. The infant was at less than the tenth percentile for length and weight for gestational age, but was otherwise healthy. Because preterm labor had occurred in this and a previously reported pregnancy in women with Bloom syndrome, increased surveillance for preterm labor in pregnancies of women with Bloom syndrome is suggested.

FOLLOW-UP

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Prognosis

• Neoplasms
• • Increased risk of premature death in the second or third decade occurs secondary to malignancies.
  • Various types of leukemia develop at a mean age of 22 years.
  • Patients who survive beyond age 22 years develop solid tumors at an average age of 35 years. Fortunately, these tumors are sensitive to chemotherapy and radiotherapy.
• Infections: Resistance to infections gradually improves with age.
• Skin: Erythema and photosensitivity improve with age.

Patient Education

• Bloom Syndrome Registry
  Laboratory of Human Genetics
  New York Blood Center
  310 East 67th Street
  New York, NY 10021
  (212) 570-3075; Fax (212) 570-3195
  Contact person: James L German III, MD

MISCELLANEOUS

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to consider this diagnosis in infants with low birthweight and in those with failure to thrive, especially if they have photosensitivity or facial erythema
• Failure to make the diagnosis or a delay in diagnosis, which can result in delayed surveillance or diagnosis of malignancies and inadequate therapy for immunodeficiency or subsequent infections

Special Concerns

• Prenatal diagnosis is possible with amniocentesis for amniotic fluid cell culture to assess for a high number of sister chromatid exchanges; DNA analysis will be available in the near future.
• Men with Bloom syndrome are sterile; women have reduced fertility and a shortened reproductive span. A 19-year-old woman with Bloom syndrome was reported with a successful pregnancy. Preterm labor occurred at 32 weeks' gestation, and the infant was ultimately delivered at 35 weeks' gestation. The infant was at less than the tenth percentile for length and weight for gestational age, but was otherwise healthy. Because preterm labor had occurred in this and a previously reported pregnancy in women with Bloom syndrome, increased surveillance for preterm labor in pregnancies of women with Bloom syndrome is suggested.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  A young patient with Bloom syndrome showing the typical photodistributed erythema on the face. Courtesy of James L. German III, MD.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• 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].

Article Last Updated: Feb 28, 2007