Bloom Syndrome – Definition

Bloom syndrome (OMIM #210900) is a rare hereditary disease associated with increased chromosomal fragility. The number of spontaneous mutations is increased and explains the increased risk of cancer. The most striking feature is significant growth retardation.

Synonyms:

BS, BSyn

Gene:

BLM

Gene ­product:

BLM DNA RecQ 3′-5′-Helicase

Function:

Part of the RECQ helicase enzymes that unwind the DNA double helix. BLM maintains genomic stability in DNA replication by limiting sister chromatid exchange (SCE).

Pattern of inheritance:

autosomal recessive

Prävalenz:

  • Unknown
  • In Ashkenazi Jews, 1 in 48,000; 0.5% heterozygosity for blmAsh

Genotype-phenotype correlation:

Homozygous and compound heterozygous carriers of one of the 60 pathogenic variants of the BLM gene exhibit a similar phenotype.

Penetrance:

Unknown

Overview of the Chapters on This Page:

  • Bloom Syndrome – Definition (This Section)
  • Bloom Syndrome – Diagnosis

  • Clinical Presentation

  • Special Features of Treatment

  • Recommendations for Early Detection in Your Patients

  • Further Information (e.g., Links to Support Groups)

  • Bloom Syndrome – Definition (This Section)
  • Bloom Syndrome – Diagnosis

  • Clinical Presentation

  • Special Features of Treatment

  • Recommendations for Early Detection in Your Patients

  • Further Information (e.g., Links to Support Groups)

Bloom Syndrome – Diagnosis

Indicative Findings

  • Unexplained severe intrauterine growth retardation that persists through infancy and childhood into adolescence.
  • Significant growth retardation and erythematous skin changes on the face after exposure to sunlight (butterfly erythema)
  • Significant growth retardation and tumor diagnosis

Diagnosis Confirmation

The diagnosis of ‘Bloom syndrome’ is confirmed by the molecular genetic detection of a biallelic/homozygous pathogenic variant in the BLM gene and/or, if the molecular genetics are unclear, by identifying an increased frequency of sibling chromatid exchanges (SCE) in special cytogenetic studies.

  • Single-gene testing
    In people with Ashkenazi Jewish ancestry, it makes sense to first analyse the most common pathogenic variant c.2207_2212delinsTAGATTC (blmAsh) (97% of all pathogenic variants are blmAsh).
  • Multi-gene panel
  • Exome/genome/mitochondrial sequencing

Differential Diagnoses

  • Russell-Silver syndrome
  • Fanconi anemia
  • Ataxia-teleangiectasia
  • Ataxia-telangiectasia-like syndrome
  • Werner syndrome
  • Nijmegen breakage syndrome

Clinical Presentation

Clinical Presentation

  • Pre- and postnatal growth retardation
  • Reduction of subcutaneous fatty tissue
  • Short stature
  • Sunlight hypersensitivity, facial erythema tendency
  • Immunodeficiency
  • Gastroesophageal reflux
  • Recurrent infections, especially of the upper respiratory tract
  • Learning disorders/reduced intelligence (not universal)
  • Premature ovarian failure in women
  • Reduced fertility/infertility in men
  • Urinary tract obstruction in men
  • Insulin resistance (diabetes mellitus type II)
  • Chronic obstructive respiratory diseases

Cancer Predisposition (Entities):

  • ALL
  • AML
  • lymphomas
  • Gastrointestinal tumors (colorectal carcinomas)
  • Germ cell tumors
  • Genital tumors
  • Tumors of the urinary tract
  • Sarcomas
  • Breast carcinoma
  • Nephroblastoma
  • Medulloblastomas
  • Retinoblastomas

Multiple tumors develop with the same distribution pattern as in the healthy population but at an earlier stage.

Special Features of Treatment

  • Avoid exposure of the face to sunlight
  • Prefer MRI and ultrasound to X-ray and CT in diagnostics
  • Hypersensitivity to ionizing radiation and DNA-damaging cytostatic drugs may require a dose reduction or shortening of the duration of therapy.

Diagnosis of Bloom Syndrome- What's Next?

Once diagnosed, it is recommended that the patient be managed by a cancer predisposition specialist. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. There is also some additional information at the end of this page, including links to support groups.

Diagnosis of Bloom Syndrome - What's Next?

Once diagnosed, it is recommended that the patient be managed by a cancer predisposition specialist. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. There is also some additional information at the end of this page, including links to support groups.

Recommendations for Early Detection in Your Patients

Evidence-based standards for early detection are lacking, especially in childhood. Below are the AACR consensus recommendations.

  • Hemato-oncology:
    • Medical history and clinical examination
    • Avoidance of radiation exposure
    • Blood count every 3-4 months
    • Breast MRI and sonography starting at 18 years of age
    • Annual colonoscopy starting at 10-12 years of age
    • Stool examination every 6 months
    • Renal ultrasound every 3 months from diagnosis until 8 years of age (screening for nephroblastoma)
    • HPV vaccination
  • Dermatology:
    • Annual skin examination
    • Limited sunlight exposure!
  • Pulmonology:
    • Pulmonologic function tests according to clinical need
    • Aggressive antibiotic therapy according to antibiogram
  • Gastroenterology/Nutrition:
    • Basic examination
    • Swallowing tests if required
    • Nutritional supplementation
  • Endocrinology:
    • Annual TSH, T3, T4
    • Annual fasting glucose and lipid profile starting at 10 years of age
  • Orthopedics:
    • Annual scoliosis examination
  • Dentistry:
    • Semi-annual check-ups

Bloom Syndrome – Further Information

Open Clinical Trials/ Registries

Bloom syndrome is also being researched in our companion projects Liquid Biopsy and ADDRess, so we encourage physicians to register their patients for this in addition to the CPS Registry.

Additional Resources