Clinical manifestations of telomere biology disorders in adults

Telomere biol ogy dis or ders (TBDs) are a spec trum of inherited bone mar row fail ure syn dromes caused by impaired telomere func tion due to path o genic germline var i ants in genes involved in telo mere main te nance. TBDs can affect many organ sys tems and are often thought of as dis eases of child hood. However, TBDs may pres ent in mid - or even late adulthood with fea tures sim i lar to but not always the same as the child hood - onset TBDs. Adult - onset TBDs are often cryp tic with iso lated pul mo nary, liver, or hema to logic dis ease, or can cer, and may lack the clas sic dis ease - defi n ing triad of abnor mal skin pig men ta tion, nail dys pla sia, and oral leukoplakia. Diagnostics include detec tion of very short leu ko cyte telo meres and germline genetic test ing. Notably, adult - onset TBDs may show telo meres in the 1st to 10th per cen tile for age, and some cases may not have an iden ti fi able genetic cause. TBD genetic eti ol ogy includes all modes of inher itance, with auto so mal dom i nant the most fre quent in adult - onset dis ease. Variable symp tom onset due to incom plete pen e trance, variable expressivity, and genetic anticipation add to the diagnostic challenges. Adult-onset TBDs are likely underrecognized, but their cor rect iden ti fi ca tion is of utmost impor tance, since affected patients are faced with numerous clin i cal com pli ca tions, includ ing but not lim ited to an increased risk of malig nan cies requir ing close sur veil lance for early detec tion. Currently lung, liver, or hema to poi etic cell trans plants are the only cura tive ther a peu tic approaches but can be com pli cated by comorbidities, despite improved med i cal care. This review high lights the chal lenges of iden ti fying adult - onset TBDs and addresses cur rently recommended clin i cal screen ing mea sures and ther apy options.