P456: Novel UBA1 variant associated with attenuated X-linked SMA phenotype

Case Presentation: The proband's past medical history is significant for prematurity at 34 weeks of gestation, global developmental delay, autism spectrum disorder, chronic constipation, and behavioral challenges around aggression, which included biting, scratching, and pinching.Language delay was first identified at his 15-month well child check.Family history is remarkable for depression, anxiety, and dyslexia in the proband's mother.Extended family history was significant for anxiety, depression, attention-deficit/hyperactive disorder, developmental delays, and ASD.Subspecialty care includes gastroenterology, developmental-behavioral pediatrics, and ophthalmology.Diagnostic Workup: First-line genetic testing included negative chromosomal microarray and negative Fragile X testing.Exome sequencing was significant for a maternally inherited heterozygous pathogenic variant in MYCBP2, c.4409dup (p.Leu1470Phefs*7) resulting in a diagnosis ofMYCBP2-related neurodevelopmental disorder.The proband had an MRI brain with and without contrast which showed a normal corpus callosum.There was a cluster of non-specific punctate white matter lesions in the right centrum semiovale that were likely related to his history of prematurity.The proband had a normal eye exam performed under sedation.Neuropsychological testing was limited in the proband due to the proband's behavior and level of activity.Results of the evaluation suggested that overall developmental, reasoning, language, visual motor integration, and adaptive skills are below age-level expectations.Neuropsychological testing was also obtained for the proband's mother and showed a largely intact profile with mild executive inefficiencies.Overall, results for testing of the proband's mother confirm that, despite having a pathogenic variant in MYCBP2, no significant cognitive impact is currently identifiable.