Stratified obstetric management for heterogeneous rare diseases: a precision medicine framework based on four genetic...

Rapid advances in genomic sequencing increasingly expose obstetricians to complex and heterogeneous genetic information in routine clinical practice. Traditional disease-specific screening models are no longer sufficient to guide decision-making across the broad spectrum of rare disorders encountered in reproductive medicine. Frontline clinicians require a universal yet clinically intuitive framework that links the biological logic of disease to the most appropriate obstetric intervention. In this review, we selected seven representative rare diseases as clinical models and reorganized them into four genetic archetypes according to inheritance pattern, age of onset, testability, and maternal-fetal risk. These archetypes illustrate distinct management pathways: targeted mid-trimester interception of de novo dominant mutations, preconception prevention of inherited late-onset tumor syndromes, early defense against highly heterogeneous recessive disorders, and recognition of current predictive blind spots in complex polygenic disease. We further emphasize that some genetic conditions pose direct and potentially life-threatening risks to the pregnant patient and therefore require a maternal protection strategy in parallel with fetal evaluation. This archetype-based framework is intended to facilitate communication between obstetricians and geneticists, improve the clinical interpretation of genomic findings, and provide a practical blueprint for precision obstetric management in the genomic era.