Prader-Willi syndrome (PWS) is a genomic imprinting disorder, which is due to the loss of a functional paternal copy of 15q11-q13. Four different genetic mechanisms can lead to PWS: a paternal deletion of the 15q11-q13 region, maternal uniparental disomy (UPD), a defect in the imprinting center, or an apparently balanced translocation disrupting the paternal copy of the PWS critical region. PWS is clinically characterized by hypotonia and feeding difficulty in early infancy, hyperphagia, and the gradual development of morbid obesity in early childhood if the diet is not strictly controlled. Unlike its sister imprinting disorder, Angelman syndrome (AS), in which epilepsy is a cardinal feature [Thomson et al., 2006], PWS has not previously been widely recognized as a disorder with an increased risk of having seizures [Cassidy and McCandless, 2005].
We recently observed that several of our PWS patients developed seizures. These seizures caused considerable anxiety in the parents of these patients, their primary care providers and even in their neurologists. This resulted in multiple emergency room visits and repeated brain imaging studies in a search for a cause of the seizures. In order to determine the characteristics and frequency of seizure disorder in PWS, we conducted a retrospective chart review of all PWS patients seen from 2000 to 2006 in our PWS multidisciplinary outpatient clinic at the University of North Carolina Hospital, an academic tertiary care hospital in North Carolina, USA. The multidisciplinary team consisted of a clinical geneticist, a pediatric endocrinologist, a dietitian, a psychologist, a physical therapist, and a genetic counselor. Patients were referred to this clinic because of a suspected or confirmed diagnosis of PWS. The clinical diagnosis of PWS in these patients was based on a consensus of the diagnostic criteria [Holm et al., 1993;Gunay-Aygun et al., 2001] and confirmed by genetic testing through a methylation study of the SNRPN gene and a karyotype with fluorescent in situ hybridization (FISH) probe hybridized to the SNRPN region, or by an analysis of the parental inheritance pattern of chromosome 15, if indicated. A presumed imprinting disorder (PID) was diagnosed by an abnormal methylation, no evidence of deletion, and a normal biparental inheritance pattern for chromosome 15.