32). Conversely, an SMS case with a deletion involving exons 5 and 6 paradoxically resulted in increased RAI1 transcript levels due to loss of the canonical stop codon, replaced by a downstream alternative (Ref. 50). These unique cases underscore the nuanced relationship between RAI1 variant types, expression levels and functional activity. They also highlight diagnostic challenges in distinguishing SMS from PTLS and suggest that clinical evaluation should consider both variant patterns and functional consequences of RAI1 dysregulation. The gene discussed is RAI1; the disease is Potocki-Lupski syndrome.