Clinical Correlates and Treatment Outcomes for Patients With Short Telomere Syndromes

Area of Science:

• Genetics
• Gerontology
• Hematology

Background:

• Short telomere syndromes (STSs) are rare genetic disorders characterized by accelerated cellular aging.
• These syndromes manifest with multisystemic complications, posing significant diagnostic and management challenges.

Purpose of the Study:

• To review a single institution's experience in diagnosing and managing inherited short telomere syndromes.
• To analyze the clinical phenotypes, genetic underpinnings, and treatment outcomes in patients with STSs.

Main Methods:

• Retrospective analysis of 17 patients diagnosed with short telomeres.
• Diagnosis confirmed by flow-fluorescence in situ hybridization (FISH) telomere lengths or pathogenic germline variants.
• Clinical data, genetic findings, and treatment responses were collected and analyzed.

Main Results:

• Genetic variations were identified in 35% of patients, involving genes like TERT, TERC, and DKC1.
• The most frequent clinical phenotypes were idiopathic interstitial pneumonia (71%), cytopenias (29%), and cirrhosis (12%).
• Overall survival was estimated at 182 months; treatments included lung transplantation, danazol therapy, and hematopoietic stem cell transplant, with varying degrees of success and complications.

Conclusions:

• Short telomere syndromes present with diverse clinical manifestations requiring a multidisciplinary care strategy.
• Organ-specific transplantation can provide clinical benefits for certain manifestations of STSs.
• Further research into optimal management strategies for these complex syndromes is warranted.