INTRODUCTION
Rare diseases are defined as any disease or condition that affects less than 200,000 people in the United States1. Because of their rarity, these conditions are difficult to diagnose and therefore, the time to diagnosis is prolonged and often involves extensive and expensive work up (i.e. the diagnostic odyssey). With a prevalence of < 1/1,000,0002, Schaaf-Yang Syndrome (SYS, OMIM #615547) caused by pathogenic variants in the MAGEL2 gene, is a rare disease with a very unspecific phenotype which overlaps with numerous other more common conditions, hence, defaulting it’s diagnosis even further. Nonetheless, with the advent of Next Generation Sequencing (NGS) and with it, broad sequencing techniques, more individuals with SYS have been identified and some phenotypic-genotypic associations have been proposed3. However, diagnosis continues to be delayed and achieved only after extensive work up has been done, without significant impact in management once diagnosis has been achieved. The rapid Whole Genome Sequencing (rWGS) protocol was developed at Nicklaus Children’s Hospital to facilitate the early diagnosis of children with rare genetic conditions to guide management strategies and improve long-term outcomes. We report two, genotypically identical but phenotypically distinct, cases of SYS diagnosed through the rWGS protocol and propose the early utilization of WGS in patients with poorly specific presentations to facilitate the diagnosis of patients with rare genetic diseases. In turn, this will allow for better understanding of these conditions and guide targeted management approaches that can positively influence health care outcomes in the acute and long term settings.
Keywords: MAGEL2, rapid Whole Genome Sequencing, phenotype-genotype association, ICU