Dyskeratosis Congenita (Zinsser-Engman-Cole Syndrome)
Dyskeratosis Congenita (Zinsser-Engman-Cole Syndrome)
Definition
Dyskeratosis congenita (DC) is a rare inherited multisystem disorder characterized by the triad of:
- Abnormal skin pigmentation
- Nail dystrophy
- Mucosal leukoplakia
Key Points
- Inheritance: X-linked recessive (most common), autosomal dominant, or autosomal recessive
- Age of onset: Typically in childhood (median age 8 years)
- Gender predilection: Males predominantly affected in X-linked form
- Associated with telomere maintenance defects
- High risk of malignant transformation
Clinical Features
Classic Triad (presents by age 10)
- Skin Changes:
- Reticulated hyperpigmentation
- Poikiloderma
- Hypopigmentation
- Typically affects neck, upper chest, and face
- Nail Dystrophy:
- Progressive nail changes
- Ridging and longitudinal splitting
- Complete nail loss possible
- Usually begins with fingernails
- Oral Leukoplakia:
- White patches on mucous membranes
- Commonly affects tongue and buccal mucosa
- High risk of malignant transformation
Additional Features
- Bone Marrow Failure:
- Primary cause of early mortality
- Typically develops by age 20
- Presents as pancytopenia
- Pulmonary Manifestations:
- Pulmonary fibrosis
- Abnormal pulmonary vasculature
- Restrictive lung disease
- Other Features:
- Epiphora (excessive tearing)
- Dental abnormalities
- Premature hair graying
- Learning difficulties
- Short stature
- Osteoporosis
- Liver abnormalities
Diagnostic Approach
Clinical Diagnosis
- Based on presence of classic triad
- Family history assessment
- Physical examination findings
Laboratory Studies
- Complete Blood Count (CBC):
- Monitor for bone marrow failure
- Track pancytopenia development
- Telomere Length Analysis:
- Flow-FISH analysis
- Typically shows very short telomeres
- Genetic Testing:
- DKC1 gene mutation analysis
- TERC and TERT sequencing
- Other telomere-related genes
Differential Diagnosis
- Fanconi Anemia
- Rothmund-Thomson Syndrome
- Pangeria
- Aplastic Anemia
- Idiopathic Pulmonary Fibrosis
Treatment and Management
Multidisciplinary Approach
- Regular monitoring by:
- Dermatologist
- Hematologist
- Pulmonologist
- Dentist
- Ophthalmologist
Specific Interventions
- Bone Marrow Failure:
- Hematopoietic stem cell transplantation
- Androgen therapy
- Growth factors
- Regular transfusions if needed
- Skin Care:
- Sun protection
- Regular skin cancer screening
- Moisturizers
- Oral Care:
- Regular dental examinations
- Oral cancer screening
- Management of leukoplakia
Surveillance
- Regular monitoring of:
- Blood counts
- Pulmonary function
- Liver function
- Growth and development
- Cancer screening:
- Skin examination
- Oral cavity inspection
- Age-appropriate cancer screening
Genetics and Pathophysiology
Genetic Basis
- Multiple Inheritance Patterns:
- X-linked (DKC1 gene)
- Autosomal dominant (TERC, TERT genes)
- Autosomal recessive (NOLA2, NOLA3 genes)
- Known Genes:
- DKC1 (dyskerin)
- TERC (telomerase RNA)
- TERT (telomerase reverse transcriptase)
- TINF2 (TIN2)
- NOP10 (NOLA3)
- NHP2 (NOLA2)
Pathophysiology
- Telomere Biology:
- Defective telomere maintenance
- Progressive telomere shortening
- Cellular senescence
- Genomic instability
- Tissue Effects:
- Affects highly proliferative tissues
- Bone marrow failure
- Mucosal vulnerability
- Skin changes
Disclaimer
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