The fetal phenotype is a trajectory, not a snapshot

Abstract

The fetal phenotype is a trajectory rather than a fixed observation: features emerge, progress, or resolve across gestation, and the anomaly present at 20 weeks is often not the anomaly present at 32. Sequence variants, however, are interpreted against the phenotype supplied when the test is requested, and phenotypic specificity carries evidence weight in variant classification. A scoping review of 59 studies combining serial prenatal phenotyping with sequence‐based testing found that a newly emergent phenotype led to a molecular diagnosis in 16 studies and a variant reclassification in 8; yet a gestational age for every phenotypic observation was reported in 2, a serial imaging protocol in 7, and a reclassification with both direction and evidence code in 1. The clinical signal is real, and the literature cannot quantify it. Five reporting practices are proposed, none of which requires new equipment or funding.