Abstracts

Rationale: Patients with germline phosphatidylinositol glycan biosynthesis class A (PIGA) related disorder have historically been categorized into one of two distinct subtypes: a severe form which is often fatal, and a less severe form. However, the increasing number of cases with features indicative of both subtypes raise the possibility of a phenotypic spectrum associated with PIGA disorder.  Methods: In order to further characterize this phenotypic spectrum, we present two patients with features of both the severe and less severe subtypes with review of phenotypes reported to date in the literature. Results: In 8-year-old patient 1, a maternally inherited PIGA pathogenic variant was discovered using exome sequencing. He presented with myoclonic epilepsy, mild intellectual disability, spastic diplegia, developmental motor delay, and autism spectrum disorder. Patient 2 is a 13-year-old with focal epilepsy, profound developmental delay, coarse facial features, severe intellectual disability and autism spectrum disorder. A de novo PIGA pathogenic variant was found through exome sequencing. Both patients had normal alkaline phosphatase levels and are without related organ abnormalities. Conclusions: As the phenotypic spectrum of PIGA mutations continues to evolve and accurate prognosis for medical providers and families is a priority, a single descriptive term depicting the condition as a continuous spectrum rather than two discrete forms better reflects the clinical picture of the disorder.  Funding: No funding