Screening for Trisomy 21 (T21) in twins is complicated by several factors: the zygosity, which cannot be established in dichorionic pregnancies with same gender twins; the biochemistry, including the dosage of pregnancy-associated plasma protein A (PAPP-A) and beta-human chorionic gonadotropin (β-hCG) in maternal blood, which is not fetus-specific and needs to be adjusted for chorionicity; and the lower rate of T21 affected fetuses in twin pregnancies, which do not allow a specific distribution of pathological serum markers [11,12,13]. This evidence concerns the gene PAPPA and trisomy 21.