LAUSR

Recently published studies have shown the feasibility of whole exome sequencing (WES) in prenatal diagnosis. As WES is not yet routinely implemented in all cases of fetal anomalies, discussions arise on which fetuses should be referred for broad genetic testing. The diagnostic yield is highest in fetal cases with multiple congenital anomalies. Therefore, recently Lord and et al suggested that WES is best performed by targeting those groups, inwhich it ismost likely to be diagnostic, allowing a high diagnostic yield. We do agree that these cases have a clear indication for WES, which will lead to a diagnosis in 15.4%, as shown by Lord et al (2019). This is important knowledge for the parents and relevant information for assessment of the recurrence risk. However, in many of such cases, a prenatal genetic diagnosis does not add significantly to decisions on pregnancy management. Eg, in case of a fetus with short extremities, a narrow thorax and polydactyly, the molecular diagnosis Ellis Van Creveld syndrome does neither change the fetal prognosis, nor perinatal management of the pregnancy. This is also supported by the paper of Lord et al, since 20/52 (38.5%) diagnoses were made in pregnancies that were terminated based solely on the ultrasound abnormalities. We think that the detection of genetic variants as a syndromic cause of fetal anomalies may be especially valuable in prenatal cases with a less severe phenotype or cases with an apparently isolated anomaly, in which a molecular diagnosis has a larger impact on decision‐making during pregnancy or neonatal management. In such cases, parents are facing difficult decisions based on an incomplete phenotype. It is well known that many syndromes have postnatal features that cannot be detected prenatally on routine or expert ultrasound scans, eg, intellectual disability or hypotonia. An example is the case of Lord et al with an atrioventricular canal defect, where a pathogenic variant in the ANKRD11 gene was detected (KBG syndrome). An intellectual disability in addition to a structural cardiac defect can significantly influence the prospective parents' decision on continuing or terminating the pregnancy. Petrovski et al 2 found a variant in the L1CAM gene in a male fetus with agenesis of the corpus callosum. In our practice, we have diagnosed several severe syndromic disorders in fetuses presenting with milder or isolated anomalies, eg, Cornelia de Lange syndrome (NIPBL) in a fetus with