Prenatal detection of Gorlin–Goltz syndrome: a case report and focused review of the literature

Introduction Gorlin–Goltz syndrome is a rare tumor-predisposing condition caused by genetic variants in the PTCH1 and SUFU pathways. The list of genetic variants associated with Gorlin–Goltz syndrome is not yet exhaustive. In this study, we present a unique case with typical features and a genetic variant previously classified as a variant of uncertain significance. Case presentation In this case, genetic testing was performed due to fetal hydronephrosis and omphalocele. Additional features included macrocephaly with hypertelorism and agenesis of the corpus callosum. Genetic testing revealed a heterozygous de novo splice-region variant, c.945 + 5G > T p.?, in PTCH1 (NM_000264.5), predicted to result in an in-frame deletion of the last 87 base pairs of exon 6. Discussion In the presence of typical prenatal features, this genetic variant was reclassified as likely pathogenic for Gorlin–Goltz syndrome. As prenatal features are often non-specific, and hydronephrosis and omphalocele are relatively common, Gorlin–Goltz syndrome should be included in the differential diagnosis during genetic testing for these fetal anomalies, particularly when additional syndromic features are present. Close interdisciplinary teamwork between prenatal ultrasound specialists and geneticists is essential to correctly evaluate non-specific fetal abnormalities and establish an accurate diagnosis in the fetus. Sometimes, as in this case, this process can lead to the reclassification of known genetic variants or even the identification of novel variants.