Walker-Warburg syndrome and tectocerebellar dysraphia: A novel association caused by a homozygous DAG1 mutation.

Abstract

To elaborate the imaging phenotype associated with a homozygous c.743C>del frameshift mutation in DAG1 leading to complete absence of both α- and β-dystroglycan previously reported in a consanguineous Israeli-Arab family. We analyzed prenatal and postnatal imaging data of patients from a consanguineous Israeli-Arab kindred harboring the DAG1 mutation. The imaging studies (fetal ultrasound, CT scan and postnatal MRI) demonstrated: flat cortex (abnormally thick with irregular pebbled cortical-white matter border on MRI), hydrocephalus, scattered small periventricular heterotopia and subependymal hemorrhages and calcifications, z-shaped brainstem, and in addition an occipital encephalocele, vermian agenesis, and an elongated and thick tectum (tectocerebellar dysraphia). The novel association of cobblestone malformation with tectocerebellar dysraphia as part of WWS is characteristic of the homozygous c.743C>del frameshift mutation in the DAG1 gene.