Down syndrome is clinically characterized by mental retardation, birth defects, and specific physical features that are identifiable at birth. Mental retardation ranges from mild to severe with most cases showing a moderate level, to evaluate the effectiveness the second-trimester soft marker sonography combined with biochemical quadriple test screening for prenatal diagnosis of triosmy 21 in patient with risk factor for down syndrome, this is a prospective cohort study that was conducted at Department of obstetrics & Gynecology ,at Benha university hospital, and carried on 80 patients ,Ultrasound was done by voluson 2d and 3d searching for a number of soft markers, that there is high significant correlation between down syndrome and Hyper echogenic fetal bowel, Nasal bone hypoplasia, Mild ventriculomegally and Enlarged cysterna magna. Also there is significant correlation between Down syndrome and Choroid plexus cyst, Intra-cardiac echogenic foci, Single umbilical artery and Mild hydronephrosis, Second‐trimester soft markers, especially a thickened nuchal fold, remain important observations in the detection of Down syndrome by sonography among fetuses who have had first‐trimester sonographic screening for aneuploidy.