D1.335 - TeloNet is born; why immunologists should know about telomere disorders

Dyskeratosis congenita (DC) are rare Telomere Biology Disorders (TBDs) caused by alterations in genes coding for molecular complexes involved in preserving telomere integrity during cell division.

Inheritance patterns include autosomal dominant (AD), autosomal recessive (AR), X-linked (XLR) or de novo. Depending on the germline variant, outcomes can alter telomere stability, trafficking of telomere components and affect protection against DNA damage/aberrant recombination events as cells divide.

TBD genes are included in Genomics England panels:  R94 Primary Immunodeficiency, R91 (cytopenia- NOT Fanconi) and R96 (interstitial lung disease).

Short telomeres are a hallmark of TBDs which produce progressive bone marrow failure and senescent/fibrotic clinical spectrum that can be multisystem, with predisposition to cancer, pulmonary and liver complications.

TBD disorders present to immunologists early, as combined immune deficiencies or in adult-hood as CVID-like disorders. Presentation can be via different specialities and may patients require lifelong multi-disciplinary monitoring, care and support.

Awareness of TBDs is low. The route to diagnosis is often long and difficult and significant under/misdiagnosis is likely.

Stem cell transplantation with non-myeloablative conditioning is required for severe disease. However, immunosuppression is likely deleterious, and late non-haematological complications are commonly fatal. Attenuated androgens preserve telomere length and may improve clinical outcomes.  

DC Action, a charity committed to supporting people living with TBDs convened the first TeloNet meeting at the Francis Crick Institute on 11th November 2024 to bring together patients, clinicians from multiple disciplines and scientists interested in TBDs.

The aim is to establish a network that will improve diagnostic pathways, facilitate co-ordinated, multidisciplinary care for patients and encourage research & sharing of clinical expertise.

DC Action anticipate regular TeloNet meetings in future to share expertise and to provide a platform for research and clinical studies into TBD conditions.

Telomere disorders may masquerade as inflammatory primary immunodeficiencies but require non-immunosuppressive treatments. 

DC Action invites immunlogists to join the TeloNet network to develop specialist services and improve care for TBD patients. Contact video abstract.