Background: Prenatal diagnosis of complete uniparental isodisomy of chromosome 4 (iUPD4) subjects has rarely been reported and poses a great challenge for genetic counseling.In this study, a prenatal case with a high (1 in 58) risk of Down syndrome was diagnosed with iUPD4 by combined chromosomal microarray analysis (CMA) , whole exome sequencing (WES) and ultrasound morphology scan.Results: CMA results indicated that no pathogenic copy number variant was detected;however, a complete maternal iUPD4 was identified in this fetus after analyzed the parental genotype results.To detect potentially autosomal recessive variants, WES was performed.Two missense and two frameshift variants were identified but predicted to be with uncertain significance;none of the mutations were definitively associated with congenital abnormality or inherited disease.In addition, detailed ultrasound morphology scan did not identify any structural abnormality, facial dysmorphisms or intrauterine growth restriction.The family history was unremarkable.The couple was counseled with the prenatal diagnostic results, and they opted to give birth to the child.No phenotypic abnormalities were observed in this child after the first year of life.Conclusion: This study provides further evidence that iUPD4 may result in a healthy livebirth, and demonstrates that the combined use of CMA, WES and ultrasound technology provides additional information for the prenatal diagnosis and clinical management of rare UPD events.