Bloom Syndrome
Bloom Syndrome (BS)
Bloom syndrome is a rare autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive facial erythema, and markedly increased predisposition to malignancy.
Key Points
- Also known as Bloom-Torre-Machacek syndrome
- Extremely rare (~300 cases reported worldwide)
- Higher prevalence in Ashkenazi Jewish population
- Characterized by genomic instability
- 100-fold increased risk of malignancy
Clinical Manifestations
Growth & Development
- Severe pre and postnatal growth deficiency
- Birth weight typically < 2300g
- Adult height rarely exceeds 150cm
- Proportionate dwarfism
- Normal head circumference (appears large for body)
- Delayed bone age
- Normal intelligence
- Feeding difficulties in infancy
Characteristic Facial Features
- Narrow face
- Prominent nose and ears
- Malar hypoplasia
- Micrognathia
- High-pitched voice
Dermatological Findings
- Photosensitive telangiectatic erythema ("butterfly rash")
- Appears in first two years
- Affects face, particularly cheeks and nose
- Worsens with sun exposure
- Café-au-lait spots
- Areas of hyper and hypopigmentation
- Poikiloderma
Immunological Features
- Recurrent infections
- Upper respiratory tract
- Middle ear
- Pneumonia
- IgA and/or IgM deficiency
- Reduced T-cell number and function
Endocrine & Reproductive
- Males:
- Usually infertile
- Oligospermia or azoospermia
- Small testes
- Females:
- Reduced fertility
- Early menopause
- Increased pregnancy complications
- Type 2 Diabetes risk increased
Genetics & Pathophysiology
Genetic Basis
- BLM gene mutation (chromosome 15q26.1)
- Autosomal recessive inheritance
- BLM protein is RecQ DNA helicase
- Essential for DNA repair
- Maintains genome stability
- Regulates homologous recombination
Molecular Mechanisms
- Increased sister chromatid exchanges (SCE)
- Diagnostic hallmark
- 10x normal rate
- Chromosomal instability
- Increased somatic mutations
- Defective DNA repair
Founder Effect
- Ashkenazi Jewish population:
- Carrier frequency ~1:100
- Common founder mutation blmAsh
Diagnosis & Workup
Diagnostic Criteria
- Clinical features
- Sister chromatid exchange analysis
- Genetic testing (BLM gene)
- Family history
Laboratory Studies
- Cytogenetic analysis
- Increased sister chromatid exchanges
- Quadriradial configurations
- Chromosomal breaks
- Immunoglobulin levels
- Complete blood count
- Metabolic panel
- Diabetes screening
Differential Diagnosis
- Fanconi anemia
- Rothmund-Thomson syndrome
- Werner syndrome
- Cockayne syndrome
- Silver-Russell syndrome
Management & Monitoring
General Care
- Regular growth monitoring
- Nutritional support
- Sun protection
- Sunscreen (high SPF)
- Protective clothing
- UV avoidance
- Immunization schedule adherence
Specialist Care
- Multidisciplinary approach:
- Clinical geneticist
- Pediatric endocrinologist
- Dermatologist
- Immunologist
- Oncologist
- Reproductive specialist
Preventive Measures
- Infection prevention
- Regular dental care
- Psychological support
- Genetic counseling
Cancer Surveillance
Cancer Risk
- Lifetime risk ~50%
- Mean age of diagnosis: 25 years
- Multiple primary cancers common
Common Malignancies
- Hematologic (acute leukemia, lymphoma)
- Carcinomas
- Colorectal
- Breast
- Skin
- Esophageal
- Sarcomas
- Wilms tumor
Surveillance Protocol
- Regular physical examinations
- Annual bone marrow examination
- Regular colonoscopy from age 20
- Breast cancer screening from age 20
- Regular dermatologic examination
- Prompt evaluation of any suspicious symptoms
