Fetal Presentation of Walker-Warburg Syndrome With a Novel POMT1 Splice-Altering Variant: Antenatal Imaging,...

Walker-Warburg syndrome (WWS) is a fatal autosomal recessive disorder characterized by brain and eye malformations, and prenatal diagnosis relies heavily on neuroimaging findings to guide targeted genetic screening. Here, we describe a distinctive second-trimester fetal imaging pattern observed in two siblings. In vivo and postmortem fetal magnetic resonance imaging demonstrated hydrocephalus, fused ventricles, hypoplastic cerebellar hemispheres, a small supraoccipital meningoencephalocele, and a recurrent hypoplastic 'Z'-shaped brainstem configuration. Whole-exome sequencing identified a homozygous deletion in POMT1 (c.123-11_123-5del), confirmed by Sanger sequencing, and RNA sequencing suggested reduced expression of exon 3. Recognition of a 'Z'-shaped brainstem on fetal MRI should raise strong suspicion for WWS associated with POMT1 mutations, prompting integrated pathological assessment and genetic testing, particularly when there is a positive family history.