OP10.09: Prenatal exome sequencing: a powerful tool to improve description of prenatal features related to genetic disorders

Prenatal exome sequencing (pES) is now commonly offered in clinical practice, identifying an additional diagnosis in around 30% of fetuses with structural defects and normal chromosomal microarray analysis (CMA). However, interpretation remains challenging due to limited prenatal data reported on genetic disorders. We conducted an ancillary study including fetuses with causal variants identified by trio-pES from the “AnDDI-Prenatome study." The prenatal phenotype of each patient was categorised into three groups (typical, uncommon, or unreported) based on comparison of these prenatal findings with those documented in the literature and public phenotype-genotype databases (ClinVar, HGMD, OMIM, and Decipher). Prenatal phenotype was typical for 38/56 fetuses (67.9%). For the other, association between genotype and phenotype was challenging because of uncommon prenatal features (absence of recurrent hallmark, rare, or unreported) were identified in 13 fetuses. We reported the first prenatal features associated with LINS1 and PGM1 variants. In addition, a double diagnosis was identified in three fetuses. Standardising the description of prenatal features, implementing longitudinal prenatal follow-up, and large-scale collection of prenatal features are essential to help pES data interpretation.