Rapid Genome Sequencing Augments Time to Diagnosis in Prader Willi Syndrome

Introduction

• Prader Willi Syndrome (PWS) is a complex disorder involving defects of imprinting at the paternal 15q11.2-q13 locus.
• Clinical features vary widely but include neonatal hypotonia, transient feeding difficulty, developmental delay/intellectual disability, hyperphagia, and dysmorphic facial features that may not be apparent in infancy.
• The average age of diagnosis varies by source but has been reported to be between 8 weeks to early childhood.
• DNA methylation analysis is the gold standard for PWS assessment, but typically takes several weeks to complete.
• Genome sequencing (GS) is a comprehensive genetic testing method that can be performed rapidly. We demonstrate in two cases here that it can detect PWS prior to clear clinical suspicion.