Population monitoring of trisomy 21: problems and approaches

Abstract

Trisomy 21 (Down syndrome) is the most common autosomal aneuploidy among newborns. About 90% result from meiotic nondisjunction during oogenesis, which occurs around conception, when also the most profound epigenetic modifications take place. Thus, maternal meiosis is an error prone process with an extreme sensitivity to endogenous factors, as exemplified by maternal age. This contrasts with the missing acceptance of causal exogenous factors. The proof of an environmental agent is a great challenge, both with respect to ascertainment bias, determination of time and dosage of exposure, as well as registration of the relevant individual health data affecting the birth prevalence. Based on a few exemplary epidemiological studies the feasibility of trisomy 21 monitoring is illustrated. In the nearer future the methodical premises will be clearly improved, both due to the establishment of electronic health registers and to the introduction of non-invasive prenatal tests. Down syndrome is a sentinel phenotype, presumably also with regard to other congenital anomalies. Thus, monitoring of trisomy 21 offers new chances for risk avoidance and preventive measures, but also for basic research concerning identification of relevant genomic variants involved in chromosomal nondisjunction.

Deep Learning-Based Architecture for Down Syndrome Assessment During Early Pregnancy Using Fetal Ultrasound Images

“…Trisomy 21 is a well-known example of aneuploid mutations, which are extensively recorded in various congenital malformation monitoring systems. One such system is the European Surveillance of Congenital Anomalies (EUROCAT), a network of approximately 40 registries based on population data, established in 1979 (Sperling et al, 2023). During the last thirty years, there have been notable progressions in the diagnosis and prenatal identification of Down syndrome.…”

“…Consequently, antenatal screening became mandatory for the detection of Down syndrome in numerous countries. As of 2021, a minimum of 76.9% of countries offered complete government funding for DS diagnostic tests (Sperling et al, 2023).…”