Abstract Background: Lethal fetal anomalies are a major contributor to stillbirth and present significant diagnostic and counseling challenges, particularly when multiple organ systems are involved. While chromosomal abnormalities are commonly implicated, monogenic disorders are increasingly recognized as underlying causes. Aim: To evaluates the spectrum of fetal malformations associated with single-gene disorders in patients with a history of stillbirth. Methods: We conducted a retrospective analysis of 269 pregnant patients with prior stillbirths who presented during a subsequent pregnancy over a 3-year period. All underwent detailed ultrasonography, revealing fetal malformations in 84 cases. Results: Invasive prenatal testing was offered to all 84; 73 patients accepted, and 11 declined. Among the 73 tested,23 cases (31.5%) were diagnosed with single-gene disorders,9(12%) cases had chromosomal abnormalities,41(56%) cases showed no identifiable genetic abnormality. Of the 23 monogenic cases, 16 had a history of recurrent stillbirth, and 7 had non-recurrent events. The affected fetuses exhibited diverse anomalies, including renal malformations, skeletal dysplasias, non-immune hydrops fetalis, and cardiac defects. Parental genetic testing confirmed inheritance patterns and facilitated recurrence risk assessment. Conclusion: Monogenic disorders are the hidden culprits behind many lethal fetal anomalies—often overlooked, yet profoundly recurrent. By pairing high-resolution prenatal imaging with precision genetic diagnostics, we unlock the potential to transform uncertainty into clarity. Early detection not only empowers families with answers but also reshapes the trajectory of future pregnancies. It’s time to bring monogenic disorders to the forefront of stillbirth prevention and redefine how we counsel, care, and prepare.
Sharma et al. (Sun,) studied this question.