Atypical Presentation of TERT-Related Dyskeratosis Congenita with Aplastic Anaemia and Cerebral Venous Sinus Thrombosis

Introduction:
Dyskeratosis congenita (DC) is an inherited telomere biology disorder associated with progressive bone marrow failure and variable multisystem involvement. Diagnosis can be challenging when mucocutaneous manifestations are absent. We describe an unusual presentation of TERT-related DC in a patient initially diagnosed with acquired aplastic anaemia, highlighting the diagnostic complexity and importance of recognising an underlying telomere disorder.

Methods:
A retrospective review of the clinical course was undertaken using medical records, laboratory findings, bone marrow examinations, and radiological investigations. The diagnostic work-up included assessment for infectious, autoimmune, thrombotic, and inherited haematological conditions, alongside telomere length measurement, next-generation sequencing (NGS), and whole-exome sequencing (WES).

Results:
A previosuly healthy 16-year-old girl presented with pancytopenia consistent with non-severe aplastic anaemia. Her clinical course was complicated by transient facial nerve palsy and suspected cerebellopontine tumour, which subsequently resolved radiologically. She later developed extensive cerebral venous sinus thrombosis despite profound thrombocytopenia and required anticoagulation. Serial bone marrow examinations demonstrated features of aplasia while excluding myelodysplastic syndrome and haematological malignancy. Investigations for infectious and autoimmune disorders, thrombophilia, and inherited red cell disorders were unrevealing. The atypical clinical course prompted extended genetic investigation. Shortened telomeres (3.99 kb), together with the identification of biallelic TERT variants and the clinical phenotype, supported the diagnosis of TERT-related dyskeratosis congenita. A concurrent ETV6 variant was also identified. Thrombopoietin receptor agonists were used to manage thrombocytopenia, followed by introduction of danazol, which resulted in complete haematological remission after 2 years of treatment. Treatment has since been discontinued, and the patient remains in remission under surveillance, thus avoiding the need for haematopoietic stem cell transplantation. 

Conclusions:
This case demonstrates that telomere biology disorders should be considered in young patients with otherwise unexplained bone marrow failure, even without classical phenotypic manifestations. Telomere length assessment and genetic testing can establish the diagnosis and influence therapeutic decision-making, especially the necessity and timing of haematopoietic stem cell transplantation.