What is the treatment for Dyskeratosis Congenita (DCld)?

Treatment of Dyskeratosis Congenita (DC)

Dyskeratosis congenita requires multidisciplinary care focused on managing bone marrow failure (the leading cause of death), monitoring for malignancies, and addressing organ-specific complications, with hematopoietic stem cell transplantation being the only curative option for bone marrow failure. 1

Core Management Principles

Baseline Evaluation and Monitoring

• Establish baseline bone marrow status with aspirate and biopsy immediately after DC diagnosis to guide subsequent monitoring 1
• Perform complete blood counts at least annually, with more frequent monitoring if cytopenias develop or worsen 1
• Conduct annual bone marrow evaluations to detect myelodysplastic syndrome (MDS) or leukemia progression, as bone marrow failure is the principal cause of premature mortality 1, 2

Hematologic Management

Androgen therapy is used for cytopenias in DC patients, though it requires careful monitoring:

• Patients receiving androgens need biannual hepatic ultrasounds and liver function tests every three months due to risk of hepatic tumors and enzyme elevation 1
• Bone marrow failure remains the leading cause of death in DC, making hematologic surveillance paramount 1, 2

Hematopoietic stem cell transplantation represents the only curative option for bone marrow failure, though outcomes must be carefully weighed against transplant-related complications in this population 1

Cancer Surveillance Protocol

DC patients face significantly elevated cancer risks requiring structured screening:

Head and Neck Cancer Screening (highest priority):

• Monthly oral self-examinations by the patient 1
• Biannual dental examinations 1
• Annual evaluation by an otolaryngologist experienced in oral cancer, beginning by age 16 years 1
• Head and neck squamous cell carcinoma represents a major mortality risk in DC 1

Gynecologic Surveillance:

• Annual gynecologic examination for women due to increased genitourinary cancer risk 1

Skin Cancer Monitoring:

• Annual dermatology examination for skin cancer screening 1
• Patients should avoid excessive UV and ionizing radiation exposure 1

Pulmonary Management

• Baseline pulmonary function tests when the patient is old enough to perform them reliably 1
• Monitor for pulmonary fibrosis development, as this represents a significant cause of morbidity 1, 2
• Pulmonary complications can progress and require ongoing surveillance 1

Genetic Counseling and Family Screening

Genetic testing is strongly recommended for DC patients and at-risk family members:

• DC exhibits X-linked, autosomal dominant, and autosomal recessive inheritance patterns depending on the gene involved 1, 2
• Telomere length testing via flow cytometry with fluorescent in situ hybridization confirms diagnosis (telomeres <1st percentile for age) 1
• At least 11 genes have been implicated (DKC1, TERC, TERT, TINF2, NHP2, NOP10, PARN, RTEL1, ACD, CTC1, WRAP53) 1, 2
• Family members who test positive for pathogenic variants require the same surveillance protocols 1

Organ-Specific Complications

Hepatic monitoring: Screen for liver fibrosis/cirrhosis, particularly in patients on androgen therapy 1

Ophthalmologic care: Address lacrimal duct abnormalities and other ocular manifestations 1

Dental care: Routine dental evaluations are essential given increased oral cancer risk and dental abnormalities 1

Critical Pitfalls to Avoid

• Do not delay bone marrow evaluation after diagnosis, as establishing baseline status is crucial for detecting progression 1
• Never skip cancer surveillance even in younger patients, as malignancies can develop in adolescence and early adulthood 1
• Avoid excessive radiation exposure (including diagnostic imaging when possible), as DC patients have impaired DNA repair mechanisms 1
• Do not assume normal telomere length excludes DC, as approximately 30% of DC patients may not have identifiable mutations in known genes despite having short telomeres 1
• Recognize that genetic anticipation occurs in telomere gene variants, resulting in earlier disease onset and potentially bone marrow failure as the initial manifestation in subsequent generations 1

Prognosis Considerations

• Bone marrow failure is the principal cause of premature mortality 1, 2
• Patients develop progressive complications including pulmonary fibrosis, esophageal stenosis, urethral stenosis, liver cirrhosis, and both hematologic and solid malignancies 1, 2
• The wide clinical heterogeneity means some patients present with isolated aplastic anemia or pulmonary fibrosis without classic mucocutaneous features 1, 2