Last updated 2mo ago
A fetus has severe ventriculomegaly on ultrasound. After birth, the infant has hypotonia, structural eye abnormalities (microphthalmia), and cobblestone lissencephaly on MRI.
AR; genes involved in O-glycosylation of α-dystroglycan (POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE)
- Dystroglycan connects to dystrophin (encoded by DMD), linking the cytoskeleton to the extracellular matrix
- Cobblestone lissencephaly (type II) - "Walk on cobblestone"
- Congenital muscular dystrophy
- Eye abnormalities (microphthalmia, retinal dysplasia)
- Hydrocephalus - "Walker has extra water"
- Most severe of the dystroglycanopathies
- Typically fatal in infancy
- Suspect with the triad of cobblestone (type II) lissencephaly, congenital muscular dystrophy, and structural eye anomalies, often with prenatal ventriculomegaly
- Markedly elevated serum CK reflects the underlying muscular dystrophy; brain MRI shows cobblestone cortex, brainstem/cerebellar hypoplasia, and hydrocephalus
- Confirm with molecular testing of the alpha-dystroglycan O-glycosylation genes (POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE), typically via a panel
- AR inheritance: 25% recurrence risk; identifying the variants enables prenatal/preimplantation testing
- No curative therapy; care is supportive given the very poor prognosis (often fatal in infancy)
- CSF shunting for symptomatic hydrocephalus; manage feeding, respiratory support, and seizures
- Multidisciplinary care with neurology, ophthalmology, and palliative care; discuss goals of care with the family
- Genetic counseling for autosomal recessive inheritance and reproductive options
"Walker-Warburg will not walk": Severe congenital anomalies mean these infants typically do not survive infancy.
"Walk on cobblestone": Walker-Warburg has cobblestone lissencephaly (type II), unlike the smooth lissencephaly in Miller-Dieker.
"Issue with Weakness, Wrinkles in brain, and Retinal anomalies in WaRburg": The three organ systems affected: muscle (weakness/congenital muscular dystrophy), brain (lissencephaly), and eyes (retinal dysplasia).