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

OBJECTIVES

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.

METHODS

We analyzed prenatal and postnatal imaging data of patients from a consanguineous Israeli-Arab kindred harboring the DAG1 mutation.

RESULTS

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).

CONCLUSIONS

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.