# Handbook of Genetic Counseling/Bloom Syndrome-1

Bloom Syndrome

## Genetics

* 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

* Ashkenazi Jewish population
* Carrier frequency 1 in 107
* Incidence 1/160,000
* Very rare in Non-Ashkenazi Jewish populations

## Diagnosis

* Characteristic clinical features
* Demonstration of symmetric QR interchange configuration and increased number
of SCEs
* Demonstration of mutations in both BLM genes

## Clinical Features

* 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
* 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

* 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

* Autosomal Recessive

## Testing

* 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

* 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

* Other syndromes associated with sun sensitivity and telangiectasias:
* Erythropoietic protoporphyria
* Rothmund-Thomson syndrome
* Cockayne syndomre
* Hereditary hemorrhagic telangiectasia
* Ataxia telangiectasia

## Psychosocial Issues

* Physical appearance may affect self-image, confidence
* Reduced life expectancy
* High probability of malignancy

## Patient Resources

* 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

* See attached

## References

* 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

The information in this outline was last updated in March 2003.