Seattle Children's

Research Overview

Human Brain Malformations

Human cerebellar malformations include Dandy-Walker malformation, cerebellar vermis hypoplasia, rhombencephalosynapsis and many others. These disorders are caused by disruptions of brain development during early embryogenesis and are often accompanied by other birth defects, including hydrocephalus and agenesis of the corpus callosum. These birth defects are relatively common, collectively affecting 1/5000 live births and can cause significant developmental delays and contribute to autism. Our studies of cerebellar malformations have lead to a more general interest in birth defects of the dorsal midline of the brain - including hydrocephalus, aqueductal stenosis, agenesis of the corpus callosum, chiari malformation and spina bidifa.

Click for more information about our Dandy-Walker and cerebellar malformation research studies.

Together with Dr William Dobyns, we maintain the world's largest clinical database of human cerebellar malformation patients and also have accompanying DNA samples. This resource has proven invaluable to find the genes that cause these relatively common, yet poorly understood birth defects. Specifically, we have defined the first causative genes for Dandy-Walker malformation. Our studies have also determined that Dandy-Walker malformation is extremely heterogeneous; genetically, multiple loci are involved and clinically, patients exhibit a spectrum of phenotypes from lesions at the same locus.