Fetal imaging, phenotyping, and genomic testing in modern prenatal diagnosis

Abstract

Genetic tests available in the prenatal setting have expanded rapidly with next generation sequencing, and fetal imaging can detect a breadth of many structural and functional abnormalities. To identify a fetal genetic disease, deep phenotyping is increasingly important to generate a differential diagnosis, choose the most appropriate genetic tests, and inform the results of those tests. The Human Phenotype Ontology (HPO) organizes and defines the features of human disease to support deep phenotyping, and ongoing efforts are being made to improve the scope of the HPO to comprehensively include fetal phenotypes. There are important limitations of fetal phenotyping to understand, including ongoing structural development and limited knowledge of how many genetic diseases present uniquely in utero. This article provides an overview of the use of HPO terms and artificial intelligence in the approach to fetal phenotyping and genetic testing.