Prenatal Deep Phenotyping in Genetic Syndromes Diagnosed in the First Trimester of Pregnancy

We perform a deep phenotyping of fetuses diagnosed with genetic syndromes in the first trimester of gestation using HPO standardized terminology.

A retrospective cohort of 293 fetuses that underwent prenatal genetic testing in the first trimester from 2020 to April 2024, in a University Reference Hospital. Descriptive and comparative analyses were performed. Statistical significance was set at p < 0.05.

More than half of fetuses had a genetic diagnosis. Chromosomal disorders were the most common (90%). Polymalformed fetuses achieved the highest diagnostic yield (73.8%). Neck anomalies HP:0025667 were the most common (68.6%). Fetuses with abnormalities of the genitourinary system HP:0000119 and abnormalities of the nervous system HP:0000707 were diagnosed with a monogenic rather than a chromosomal disorder, p < 0.001. Ductus venosus agenesis HP:0034196 was frequent in Trisomy 21 as well as in RASopathies.

We highlight the utility of the HPO terms in standardizing phenotypic descriptions and improving the diagnosis of genetic syndromes in the first trimester. Although each disorder has different and non-specific affected organ systems, there is a tendency for some organs to be more frequently affected in some conditions. Agenesis of ductus venosus arises as a potential finding in the first trimester for RASopathies.