anticipation

Anticipation occurs in trinucleotide repeat expansion disorders, where the number of repeated nucleotide sequences (e.g., CAG, CTG, CGG) within or near a gene increases with each generation due to slippage during DNA replication, particularly during meiosis. This expansion can occur more readily during spermatogenesis (e.g., Huntington disease) or oogenesis (e.g., Fragile X syndrome), depending on the disorder. As the repeat number increases, the disease often presents earlier and with greater severity in subsequent generations. Key examples tested on boards include: Huntington disease (CAG repeat, autosomal dominant, expansion via paternal transmission), Myotonic dystrophy type 1 (CTG repeat, autosomal dominant), Fragile X syndrome (CGG repeat, X-linked, expansion via maternal transmission), and Friedreich ataxia (GAA repeat, though this one is unusual in that it doesn't always show anticipation and is autosomal recessive). Clinically, anticipation explains why later-generation family members may be diagnosed at younger ages with more severe symptoms, which is important for genetic counseling and family history-taking. Understanding trinucleotide repeat number thresholds (premutation vs full mutation) is especially relevant for Fragile X syndrome, where premutation carriers can be asymptomatic but their offspring may inherit an expanded, disease-causing repeat.