For individuals presenting with the classic CdLS phenotype, the recommended first-line molecular diagnostic strategy is Next-Generation Sequencing (NGS)–based analysis, such as Whole-Exome Sequencing (WES) or Whole-Genome Sequencing (WGS), with particular attention to the NIPBL, SMC1A, SMC3, RAD21, BRD4, HDAC8, and ANKRD11 genes. The gene discussed is SMC1A; the disease is Cornelia de Lange syndrome.