Definition
Dyskeratosis congenita (OMIM: #127550, #30500, #615190, #613987, and #613989) is a telomeropathy characterized by the classic clinical triad of nail dystrophies, oral leukoplakia, and pigment disorders affecting the upper thoracic aperture and the cervical region. There is an increased risk of progressive bone marrow failure and the development of myeloid neoplasia, solid tumors, and pulmonary fibrosis. The clinical symptoms vary, and often lack the classic triad.
Key Data
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Synonyms | DC, telomere syndromes, Zinsser-Cole-Engman syndrome |
Genes | ACD, CTC1, DKC1, NHP2, NOP10, PARN, RTEL1, TERC, TERT, TINF2, WRAP53 (30% of cases with clinical DC have not yet been genetically classified to date) |
Gene products | All gene products play a role in telomere biology. TERC encodes an RNA. |
Function | Stability and maintenance of telomeres, which in turn are essential for chromosomal stability |
Heredity |
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Prevalence | At least 400 families around the world in 2015 |
Genotype-phenotype correlation | Extensive studies are lacking. Severe progressions (shorter telomeres than classic DC):
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Penetrance | Currently not very well understood. High degree of inter-individual and intra-familial variations with an age-dependent onset of symptoms; penetrance appears to be incomplete. Anticipation phenomenon. |
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Diagnosis
Classic DC Diagnostic Triad (Not Present in All DC Patients)
Diagnostics
Differential Diagnoses
Clinical Presentation
Typical Presentation
Severe Progressions
Krebsprädisposition
The risk of a malignant disease is 11 times higher compared to the healthy population. Onset from the third decade of life.
Therapeutic Considerations
Surveillance Recommendations
Surveillance Recommendations
Evidence-based standards for tumor screening and clinical management are lacking due to the rarity of the disease. The following are the recommendations from the AACR consensus meeting in October 2016.
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Hematology-oncology |
Medical history and physical examination, annual blood count, annual bone marrow puncture and punch biopsy if corresponding clinical symptoms have been diagnosed, early referral to a transplant center, HPV vaccination, annual ENT checkups as of adolescence, (HNSCC evaluation) |
Immunology |
Monitoring of the immunoglobulin levels according to immunological recommendations |
Dermatology |
Annual skin screening |
Pulmonology |
Baseline function testing with regular routine follow-up |
Gastroenterology and nutrition |
Annual liver function testing, more frequently in tandem with androgen therapy (six-monthly hepatic ultrasound, three-monthly liver function testing) |
Endocrinology |
Annual screening for diabetes, growth monitoring |
Neurology |
cMRT examination for cerebellar hypoplasia if a diagnosis has been made, early supportive therapy in the event of developmental retardation |
Ophthalmology |
Annual examinations, monitoring, and early intervention in the event of lacrimal duct stenosis |
Orthopedics |
Evaluation of aseptic bone necrosis of the hip and shoulder according to clinical symptoms |
Dental |
Six-monthly checkups |
ENT |
Baseline hearing status |
Cardiology |
Baseline evaluation for AV and cardiac malformations |
Urogenital tract |
Baseline examination for urogenital malformations |
Gynecology |
Annual examination |