Handbook of Genetic Counseling/Bloom Syndrome-1
Bloom Syndrome
Genetics
edit- Mutation of BLM gene at chromosome 15q26.1
- Common Ashkenazi Jewish mutation- blmASH (2281del6ins7)
- Abnormalities in DNA repair and chromosomal structure
- increased chromosome breakage
- increased rate of homologous chromosome exchange
- formation of quadriradial (QR) configuration in mitosis
- increased rate of sister chromatid exchanges (SCEs)
- unique to Bloom Syndrome
Incidence
edit- Ashkenazi Jewish population
- Carrier frequency 1 in 107
- Incidence 1/160,000
- Very rare in Non-Ashkenazi Jewish populations
Diagnosis
edit- Characteristic clinical features
- Demonstration of symmetric QR interchange configuration and increased number
of SCEs
- Demonstration of mutations in both BLM genes
Clinical Features
edit- Predominant features
- Small body size
- Mean birth weight 1906 g in males and 1810 g in females
- Mean adult height 147.5 cm in males and 138.6 cm in females
- Predisposition to cancer- of all cell types and at all sites
- Small body size
- Additional features which may or may not be present
- Characteristic facies- keel-shaped face, dolicocephaly, narrow cranium, malar hypoplasia, nasal prominence, small mandible, and prominent ears.
- Hypersensitivity to sunlight- formation of sun-sensitive erythema (telangiectasia) on face and possible hands/forearms
- Areas of hyper- and hypo- pigmented skin- café-au-lait spots
- High-pitched and somewhat squeaky voice
- Vomiting and diarrhea during infancy
- Diabetes mellitus- generally with onset in the second or third decade
- Failure of spermatogenesis in males
- Early cessation of menstruation and reduced fertility in females
- General immunodeficiency- often associated with ottitis media and pneumonia
- Slightly increased incidence of minor anatomic anomalies including anomalous digits, pilonidal dimples, wedges of altered color of the irides, and obstructing anomalies of the urethra
- Restricted intellectual ability- generally average to low-average intelligence but can be more severe
Natural History
edit- Intrauterine Growth Deficiency
- full-term infants tend to have low birth weight
- Onset of facial skin lesion usually in first or second summer, can be later
- Cancer predisposition throughout life- always higher than age-associated risk
- Mean age of cancer diagnosis 24.7 (range of 2 to 48 years)
- Mean age of death is 23.6 years (range from <1 to 49)
- Cancer is the most common cause of death
Inheritance
edit- Autosomal Recessive
Testing
edit- Cytogenetic analysis
- Increased in number or chromatid gaps, breaks, and interchanges
- Increase in the number of sister-chromatid exchanges (SCEs)
- Can be performed on any cell which can be brought into mitosis
- Molecular Genetic Analysis
- Clinical testing for common Ashkenazi Jewish mutation- blmASH
- 98% detection for Ashkenazi Jewish Bloom syndrome patients
- Research testing - full gene screening for affected individuals
- Memorial Sloan-Kettering Cancer Center
- Prenatal diagnosis
- Sister chromatid exchange assay via amnio or CVS
- Amnio or CVS for known familial mutation
Management & Treatment
edit- No treatment for growth deficiency
- Protection from the sun decreases severity of skin lesion
- Careful monitoring for cancer
- Cancer treatment must consider hypersensitivity to DNA-damaging chemicals
Differential Diagnosis
edit- Other syndromes associated with sun sensitivity and telangiectasias:
- Erythropoietic protoporphyria
- Rothmund-Thomson syndrome
- Cockayne syndomre
- Hereditary hemorrhagic telangiectasia
- Ataxia telangiectasia
Psychosocial Issues
edit- Physical appearance may affect self-image, confidence
- Reduced life expectancy
- High probability of malignancy
Patient Resources
edit- Bloom's Syndrome Registry
- NY Blood Center
- 310 East 67th Street
- New York, NY 10021
- Phone: (212) 570-3075
- National Foundation for Jewish Genetic Diseases, Inc. (NFJGD)
- 250 Park Ave, Suite 1000
- New York, NY 10177
- Phone: (212) 371-1030
- Web
- Xeroderma Pigmentosum Society, Inc.
- Box 4759
- Poughkeepsie, NY 12602
- Phone: (518) 851-2612
- Web
- E-mail: xps@xps.org
Case Specifics
edit- See attached
References
edit- Byarlay, J. and Goldsmith, L. (1997) Other Genetic Disorders of the Skin. In Rimoin, D, Connor, J, and Pueritz, R ed. Principles and Practice of Medical Genetics. Churchill Livingstone: New York. 1309-1310.
- German, J. and Ellis, N. (2001). Bloom Syndrome. In Scriver, C., Beaudet, A., Sly, W., and Velle, D. ed. Metabolic and Molecular Bases of Inherited Disease. McGraw Hill: New York. 733-751.
- Goodman, R. (1979) Genetic Disorders among the Jewish People. Johns Hopkins
University Press: Baltimore. 73-79.
Notes
editThe information in this outline was last updated in March 2003.