Recognizing repeat expansion disorders in clinical practice

Repeat expansion disorders are caused by unstable DNA sequences that exceed pathogenic thresholds, disrupting normal gene function. These conditions often affect the nervous system, but may involve multiple organs, with presentations ranging from subtle cognitive or motor changes to overt neuromuscular or neurodevelopmental syndromes. Early symptoms can mimic common conditions, making clinical suspicion, family history, and awareness of intergenerational patterns essential. Molecular features, including repeat size, sequence, location and stability, determine disease severity and variability. Nurse practitioners are well positioned to recognize early signs, make early referrals to genetics, and support families with education, anticipatory guidance, and coordination of follow-up care. Case examples include Huntington disease, fragile X syndrome, and myotonic dystrophy and illustrate clinical heterogeneity, premutation effects, and genetic anticipation. Early recognition and referral remain crucial, particularly as emerging gene-targeted therapies may offer potential disease-modifying options.