Prenatal phenotyping: A community effort to enhance the Human Phenotype Ontology

Ferdinand Dhombres, Patricia Morgan, Bimal P. Chaudhari, Isabel Filges, Teresa N. Sparks, Pablo Lapunzina, Tony Roscioli, Umber Agarwal, Shagun Aggarwal, Claire Beneteau, Pilar Cacheiro, Leigh C. Carmody, Sophie Collardeau-Frachon, Esther A. Dempsey, Andreas Dufke, Michael Henri Duyzend, Mirna el Ghosh, Jessica L. Giordano, Ragnhild Glad, Ieva GrinfeldeDominic G. Iliescu, Markus S. Ladewig, Monica C. Munoz-Torres, Marzia Pollazzon, Francesca Clementina Radio, Carlota Rodo, Raquel Gouveia Silva, Damian Smedley, Jagadish Chandrabose Sundaramurthi, Sabrina Toro, Irene Valenzuela, Nicole A. Vasilevsky, Ronald J. Wapner, Roni Zemet, Melissa A. Haendel, Peter N. Robinson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care.

Original languageEnglish
Pages (from-to)231-242
Number of pages12
JournalAmerican Journal of Medical Genetics, Part C: Seminars in Medical Genetics
Issue number2
StatePublished - Jun 2022
Externally publishedYes


FundersFunder number
Australian Federal Government Medical Research Futures Fund
European Union's EIT-Health
European Union's EIT‐Health Innovation Program bp2020‐2022
MRFFPI 20/01053
SUOG-Smart Ultrasound in Obstetrics and Gynecology
SUOG‐Smart Ultrasound in Obstetrics and GynecologyFIS‐ISCIII PMP21/00063
National Institutes of Health
National Human Genome Research InstituteU24HG011449, 2R24OD011883‐05A1
NIH Office of the Director
British Heart FoundationFS/18/78/33932
European Commission20062, 211015
Horizon 2020779257


    • GA4GH Phenopacket
    • HPO
    • fetal pathology
    • human phenotype ontology
    • prenatal diagnosis
    • prenatal phenotyping


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