Abstract
Tandem repeat disorders (TRDs) are genetic conditions characterized by the abnormal expansion of repetitive DNA sequences within specific genes. The growing number of identified TRDs highlights their complexity, with varied molecular mechanisms ranging from toxic protein production and repeat-associated non-AUG translation to RNA toxicity and epigenetic modifications. TRDs also exhibit unique clinical features such as reduced penetrance, anticipation, and repeat motif changes. Advances in molecular diagnostics such as long-read sequencing have significantly improved the detection of TRDs, especially for large or complex repeat expansions. Additionally, emerging therapeutic strategies, particularly antisense oligonucleotides (ASOs) and gene editing technologies, are showing great promise. ASOs in particular have demonstrated success through mechanisms like allele-specific knockdown and splice modulation. In this review, we explore the classification of TRDs, advances in diagnostics, molecular mechanisms, clinical features, and innovative therapeutic strategies, highlighting the need for further research to refine treatments and improve outcomes.