22q11.2 deletion syndrome: the case for routine prenatal genetic screening

Cell-free DNA (cfDNA) screening has become a standard non-invasive prenatal genetic screening method for aneuploidies, with optional inclusion of selected chromosomal microdeletions available in the last decade. The most common pathogenic microdeletion defines the 22q11.2 deletion syndrome (22q11.2DS) that is characterized by congenital cardiac and other anomalies, endocrinological/metabolic conditions, and/or neurodevelopmental deficits/disorders. The deletion presents in 90% of cases as a spontaneous ( de novo ) genetic change, regardless of parental age. 22q11.2DS meets the criteria for prenatal screening: a well understood condition with significant early morbidity, effective treatments, and benefits of screening outweighing risks. cfDNA screening demonstrates positive predictive values ranging from 52.6% in a general population to >90% in screening of high-risk (ultrasound-finding enriched) cohorts. Through partnerships with the genetics community and with informed primary care teams, the data now support offering cfDNA screening for 22q11.2DS to all pregnant patients.