Prenatal Detection of TGFBR1 Variant Associated With Severe Ventriculomegaly and Loeys-Dietz Syndrome

To report a novel prenatal presentation of Loeys-Dietz Syndrome type 1 (LDS1), characterized by severe ventriculomegaly and macrocephaly, associated with a likely pathogenic variant in the TGFBR1 gene.

A 31-year-old G4P2012 was referred for fetal ventriculomegaly identified during routine first-trimester ultrasound. Comprehensive fetal evaluation included serial imaging, fetal echocardiography, and whole genome sequencing. Genetic counseling and multidisciplinary care were provided throughout the pregnancy.

Imaging confirmed progressive, severe ventriculomegaly without evidence of neural tube defect or cardiac abnormality. Whole genome sequencing revealed a novel de novo heterozygous c.689C>A, p.(Ala230Asp) variant in TGFBR1, classified as likely pathogenic. The patient underwent cesarean delivery at 37w1d due to significant macrocephaly. Postnatal findings included Dandy-Walker malformation requiring ventriculoperitoneal shunt, unilateral retinal detachment, and focal seizures. Postnatal echocardiogram was normal. Dysmorphic features and clinical findings were consistent with LDS1.

This case expands the prenatal phenotype associated with Loeys-Dietz Syndrome type 1, demonstrating that severe ventriculomegaly and macrocephaly may be early markers of disease. Early identification of LDS1 through advanced prenatal imaging and genetic testing may support anticipatory guidance and multidisciplinary care planning.