Foundations · Year 1 · from Foundations
Case 3: Dyskeratosis Congenita (Telomere Disorder)
Clinical Image
Source: Wikipedia - Dyskeratosis congenita - CC BY-SA 3.0
Case Presentation
A 15-year-old boy is referred for evaluation of pancytopenia. He has a history of nail dystrophy since early childhood and white patches in his mouth (oral leukoplakia). His skin shows abnormal reticular pigmentation on the neck and upper chest. Complete blood count reveals hemoglobin 9.2 g/dL, WBC 2,800/mm3, and platelets 62,000/mm3. Bone marrow biopsy shows hypocellularity consistent with aplastic anemia. Given the mucocutaneous triad (nail dystrophy, oral leukoplakia, abnormal skin pigmentation) combined with bone marrow failure, dyskeratosis congenita (DC) is suspected. Telomere length analysis by flow-FISH shows severely shortened telomeres (below the 1st percentile for age). Genetic testing identifies a mutation in TERT, encoding the catalytic component of telomerase. Without adequate telomerase activity, telomeres shorten prematurely with each cell division. Stem cells, which must divide many times, are particularly affected, explaining the bone marrow failure. He is also at increased risk for pulmonary fibrosis and solid tumors. He is evaluated for hematopoietic stem cell transplantation and counseled about the need for modified conditioning regimens given his underlying DNA repair defects.
Key Learning Points
- Telomeres are repetitive TTAGGG sequences that protect chromosome ends; telomerase, a reverse transcriptase with an RNA template, maintains telomere length in germ cells and stem cells
- Dyskeratosis congenita results from mutations affecting telomerase (TERT, TERC) or telomere maintenance proteins (DKC1, TINF2), causing premature telomere shortening
- Stem cells with limited replicative capacity lead to bone marrow failure, pulmonary fibrosis, and liver disease; the mucocutaneous triad (nail dystrophy, oral leukoplakia, skin pigmentation) is the classic presentation