Abstract
Introduction: Whole-exome sequencing has led to the discovery of new genes involved in developmental delay. Two of these are the evolutionary linked proteins phosphofurin acidic cluster sorting protein 1 (PACS1) and phosphofurin acidic cluster sorting protein 2 (PACS2), which function as metabolic switches. We present a case of a patient with the previously described PACS2 c.624G>A; p.Glu209Lys variant, with distinct clinical features, suggesting an overlap between the two conditions. Case Presentation: The patient presented with infantile epilepsy, developmental delay, and cerebellar hypoplasia previously described with PACS2. However, he also had novel features not noted in the literature before; this included anal atresia, tetralogy of Fallot, and vertebral abnormalities. This constellation of features had given him a label of VACTERL. Conclusion: Cardiac abnormalities are more commonly seen in PACS1 variants, and this case strengthens the phenotypic similarities between the two conditions. We also explore the genetic mechanisms causing the cardiac and anal anomalies seen in our patient and suggest the PACS2 disease spectrum should be expanded.
