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
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
Below you will find the recommendations from the 2024 Guidelines of the AACR.
Haemato-Oncology
- Good sun protection and avoidance of ionising radiation
- HPV vaccination
- Attention to tumor-related symptoms
- Clinical examination yearly from diagnosis
- Abdominal ultrasound from diagnosis every 3 months until 8 years of age may be considered
- From 10-12 years of age, annual colonoscopy and iFOBT (immunological faecal occult blood test) every 6 months
- Breast MRI yearly from age 18
Dermatology
- Annual skin check
- Limited exposure to sunlight!
Pulmonology
- Pulmonary function tests as clinically indicated
- Aggressive antibiotic therapy based on antibiogram
Gastroenterology/Nutrition
- Basic examination
- Swallowing tests if necessary
- Nutritional supplementation
Endocrinology
- Annual TSH, T3 and T4
- Annual fasting glucose and lipid profile from 10 years of age
Orthopaedics
- Annual scoliosis screening
Dentist
- Semi-annual checks
