Dyskeratosis congenita

Dyskeratosis congenita (DC), also known as Zinsser-Engman-Cole syndrome, is a rare inherited bone marrow failure syndrome caused by defective telomere maintenance. The disease results from mutations in genes involved in the telomerase complex and telomere biology, leading to critically shortened telomeres that impair the ability of cells to divide and renew. DC classically presents with a triad of mucocutaneous features: abnormal skin pigmentation (reticulate hyperpigmentation, particularly of the neck and upper chest), nail dystrophy (ridging, splitting, or absent nails), and oral leukoplakia (white patches in the mouth). However, the disease affects multiple organ systems beyond the skin. Bone marrow failure is the most serious complication and the leading cause of morbidity and mortality, occurring in approximately 80–90% of patients. Patients are also at significantly increased risk for pulmonary fibrosis, liver disease (hepatic fibrosis and cirrhosis), and predisposition to certain cancers, particularly myelodysplastic syndrome, acute myeloid leukemia, and squamous cell carcinomas of the head, neck, and anogenital region. Other features may include epiphora (excessive tearing due to blocked tear ducts), developmental delay, esophageal stenosis, urethral stenosis, and osteoporosis. A severe variant known as Hoyeraal-Hreidarsson syndrome presents in early childhood with cerebellar hypoplasia, immunodeficiency, and intrauterine growth restriction, while Revesz syndrome includes bilateral exudative retinopathy. Treatment is primarily supportive and depends on the specific complications. Bone marrow failure may be managed with androgens (such as danazol, which can transiently increase telomerase activity and improve blood counts) and hematopoietic growth factors. Hematopoietic stem cell transplantation (HSCT) remains the only curative option for the bone marrow failure component, though patients with DC are at higher risk for transplant-related complications, particularly pulmonary and hepatic toxicity, necessitating reduced-intensity conditioning regimens. Surveillance for cancer and organ-specific complications is essential. Genetic counseling is recommended given the hereditary nature of the condition.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Dyskeratosis congenita