Intracranial abnormalities detected by three-dimensional magnetic resonance imaging in Prader-Willi syndrome

The neuropathologic abnormalities associated with Prader-Willi syndrome (PWS) are largely unknown. PWS is due to the loss of several paternally expressed genes in chromosome 15q11-q13 region. Several of the imprinted genes in the 15q11-q13 region are normally expressed in the brain and thought to be necessary for neuronal growth and development. Thus, we hypothesized that we would find abnormalities in gray and white matter growth in individuals with PWS. We evaluated three-dimensional (3-D) MRI scans of 20 individuals with PWS, aged three months to 39 years, and compared them to 3-D MRI scans of 21 normal weight sibling controls and 16 individuals with early-onset morbid obesity (EMO) of unknown etiology. The interpreters of the scans were blinded to the diagnosis of the subjects. Intracranial abnormalities in individuals with PWS included ventriculomegaly (100% of individuals), decreased volume of brain tissue in the parietal-occipital lobe (50%), sylvian fissure polymicrogyria (60%), and incomplete insular closure (65%). None of the EMO or normal weight control subjects had any of these findings. We found multiple morphologic brain abnormalities in subjects with PWS suggesting that the loss of paternally expressed genes in chromosome 15q11-q13 region may result in abnormalities of neuronal development. The specific mechanisms underlying these neuropathological abnormalities and their correlation with the clinical phenotype remain to be elucidated.