RESUMO
OBJECTIVE: The objectives of this study were to characterise genotype-phenotype discordance identified in the routine clinical setting and to explore the associated diagnostic and counselling challenges. METHOD: Cases were derived from a cohort of pregnant women who attended a multisite specialist prenatal screening and ultrasound service for non-invasive prenatal testing by cell-free DNA analysis and midtrimester fetal morphology assessment. RESULTS: Seven cases of genotype-phenotype discordance were identified from a cohort of 12 919 women between June 2013 and March 2017 (incidence 1/1845 pregnancies). A variety of disorders of sexual differentiation were subsequently diagnosed. CONCLUSION: Sex chromosomes are the basis of sexual differentiation during embryonic development. Variations of the traditional XX or XY karyotype may result in conditions where the genotype is discordant with the phenotype. Detection of these conditions in the past typically occurred during adolescence, due to delayed puberty, or during adulthood, due to infertility. With the increasing availability of non-invasive prenatal testing and high-resolution ultrasound, more cases of genotype-phenotype sex discordance are being identified in routine clinical practice during early pregnancy. These discordant results present significant diagnostic and counselling challenges, and their potential should be included in increasingly complex pre-NIPT counselling.