Definition
Bloom syndrome (OMIM #210900) is a rare hereditary disease associated with increased chromosome breakage. The number of spontaneous mutations is elevated, thereby explaining the increased cancer risk. The most distinctive symptom is significant growth restriction.
Key Data
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Synonyms | BS, BSyn |
Gene | BLM |
Gene product | BLM DNA RecQ 3′-5′ helicase |
Function | Part of the RECQ helicases that unwind the DNA double helix. BLM maintains genomic stability during the process of DNA replication by limiting sister chromatin exchange (SCE). |
Heredity | Autosomal recessive |
Prevalence | Unknown 1:48.000 in Ashkenazi Jews; 0.5% heterozygosity for the blmAsh mutation |
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 |
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Diagnosis
Indicative Findings
Unexplained severe intrauterine growth restriction that persists throughout infancy and childhood until adolescence.
Significant growth deficit and erythematous skin changes in the face after exposure to sunlight (butterfly rash)
Significant growth deficit and tumor diagnosis
Confirming the Diagnosis
The diagnosis of “Bloom syndrome” is confirmed by molecular genetic evidence of a biallelic/homozygous pathogenic variant of the BLM gene and/or, if the molecular genetics are inconclusive, by the identification of an increased frequency of sister chromatid exchanges (SCE) by specific cytogenetic studies.
Single-gene testing
In individuals of Ashkenazi-Jewish descent, it is helpful to start with a specific analysis of the most frequent pathogenic variant: c.2207_2212delinsTAGATTC (blmAsh) (97% of all pathogenic variants are blmAsh).Multiple-gene panel
Exome/genome/mitochondrial sequencing
Differential Diagnoses
Russell-Silver syndrome
Fanconi anemia
Ataxia telangiectasia
Ataxia telangiectasia-like syndrome
Werner syndrome
Nijmegen breakage syndrome
Clinical Presentation
Clinical Presentation
Prenatal and postnatal growth restriction
Reduction of subcutaneous fatty tissue
Dwarfism
Hypersensitivity to sunlight, tendency towards facial erythema
Immunodeficiency
Gastroesophageal reflux
Recurring infections, especially in the upper airways
Learning disorders / low intelligence (not universal)
Premature ovarian insufficiency in women
Reduced fertility / infertility in men
Urinary tract obstruction in men
Insulin resistance (type II diabetes mellitus)
Chronically obstructive airway diseases
Predisposition to Cancer (Entities):
ALL
AML
Lymphomas
Gastrointestinal tumors (colorectal carcinomas)
Germ cell tumors
Genital tumors
Tumors of the urinary tract
Sarcomas
Mammary carcinoma
Nephroblastomas
Medulloblastomas
Retinoblastomas
Multiple tumors develop with the same distribution pattern as in the healthy population but with an earlier onset.
Therapeutic Considerations
Avoid exposing face to sunlight
MRI and ultrasound preferred for diagnosis over X-ray and CT
Hypersensitivity to ionizing radiation and DNA-damaging cytostatics also requires a reduction in doses or a shortening of the duration of therapy.
Surveillance Recommendations
Surveillance Recommendations
Evidence-based standards are lacking for early detection, particularly during childhood. The AACR consensus recommendations are listed below.
Hematology-oncology:
- Medical history and clinical examination
- Avoid exposure to radiation
- Blood count every 3-4 months
- Fully-body MRI every 1-2 years as of age 12-13
- Breast MRI and ultrasound as of age 18
- Annual colonoscopy as of age 10-12
- Stool test every 6 months
- Renal ultrasound every 3 months after diagnosis until age 8 (screening for nephroblastoma)
- HPV vaccination
Dermatology:
- Annual skin examination
- Limit exposure to sunlight!
Pulmonology:
- Pulmonary function testing according to clinical need
- Aggressive antibiotic treatment after an antibiogram
Gastroenterology/Nutrition:
- Basic examination
- Swallowing tests as needed
- Dietary supplementation
Endocrinology:
- Annual TSH, T3, T4
- Annual glucose test on an empty stomach and a lipid profile from 10 years of age
Orthopedics:
- Annual scoliosis examination
Dental:
- Six-monthly checkups