Binder Phenotype: Evaluating the Utility and Influence of Genetic Results on Parental Decision Making in Antenatally Diagnosed Cases

The prognosis in Binder phenotype is influenced by underlying etiology and associated findings. Genetic testing till date has focused on chromosomal anomalies and targeted testing of genes like ARSL (previously ARSE). The aim of this study was to assess the utility of exome sequencing in fetuses with antenatal Binder phenotype and explore how its results influence parental reproductive decision-making. This retrospective study included 50 fetuses with sonographic features of Binder phenotype who underwent exome sequencing with copy number variant calling. Semi-structured follow-up interviews were conducted with families to understand the rationale behind reproductive decisions. Pathogenic or likely pathogenic variants were detected in four cases, while phenotypically relevant variants of uncertain significance were observed in six additional cases. Notably, variants in GNPTAB, a novel association, were identified in two unrelated cases. Of the 31 families who awaited test results, 20 continued the pregnancy, while 7 chose termination despite negative or uncertain findings. Overall, 55% of pregnancies were electively terminated, driven by variant findings, ultrasound severity, recurrence, or previous outcomes. Genetic testing provided meaningful insights in select cases, but reproductive decisions were influenced by a broader range of clinical and psychosocial factors. We conclude that exome sequencing can support but does not dictate prenatal decision-making.