When the clinical picture suggests SMC1A involvement (early-onset, drug-resistant seizures with developmental impairment or CdLS-like features), begin with a clinician-directed multigene NGS panel or trio WES/WGS; panels optimized for epilepsy/CdLS usually afford the best balance of coverage and interpretability, while exome/genome sequencing is preferable for atypical presentations. Here, SMC1A is linked to Cornelia de Lange syndrome.