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
of SCEs
 * Characteristic clinical features
 * Demonstration of symmetric QR interchange configuration and increased number
 * 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