Prenatal diagnosis of Donnai–Barrow syndrome (LRP2-related) following recurrent fetal structural anomalies in a consanguineous family: a clinical report

To report the prenatal diagnosis of Donnai–Barrow syndrome in a consanguineous family with recurrent fetal structural anomalies. A 22-year-old gravida 4, para 3 woman was referred at 23 weeks because ultrasound showed agenesis of the corpus callosum, hypertelorism, nasal bone hypoplasia, abnormal facial profile, and diastematomyelia. Owing to recurrent similarly affected pregnancies and consanguinity, amniocentesis and prenatal whole-exome sequencing were performed. A homozygous pathogenic LRP2 frameshift variant, c.13139dupG (p.Cys4381Metfs*12), was identified; both parents were heterozygous carriers. The pregnancy was terminated, and postmortem examination showed midface hypoplasia, depressed nasal bridge, downslanting palpebral fissures, and limb anomalies. Donnai–Barrow syndrome should be considered when midline brain anomalies coexist with craniofacial dysmorphism, particularly in consanguineous or recurrently affected families. Prenatal exome sequencing enables timely molecular diagnosis and reproductive counseling.