Telomere biology disorders: recognizing the underrecognized through the lens of clinical genetics

Telomere biology disorders (TBD) is an inherited disease that causes accelerated telomere shortening leading to bone marrow failure, lung fibrosis and/or malignancy. Growing evidence of specific management especially in transplant medicine has warranted clinicians across multiple specialties to improve the diagnostic workflow of TBD. This review aims to address the bottleneck to increase the screening uptake of TBD.

The availability of genetic testing has further expanded the clinical spectrum of TBD. Correspondingly, the indications to screen for TBD, especially prelung transplantation, have grown. Methods to measure chromosome-specific telomere length have emerged, meanwhile the uptake of long-read sequencing has increased. Curative treatment of TBD remains unavailable with an ongoing clinical trial in nucleoside and gene therapy.

As phenotypic spectrum of TBD is expanding, pediatricians should be aware of growing clinical indications, especially in prior to organ transplantation. A combination of genetic testing and telomere length measurement (flow-FISH method) should be considered for screening of TBD. Multidisciplinary approach is the cornerstone of management of TBD and referral to high-volume center with experience in TBD is warranted.