Cornelia De Lange syndrome occurs in 60% of cases when there is a mutation in the NIPBL gene. In just 10% of cases, the mutation occurs on the SMC1A, SMC3, HDAC8, or RAD21 genes. 30% of cases have an unknown cause.
The majority of mutations are de novo meaning they are the first occurring case within a family. You can learn more here: https://fdna.health/syndromes/cornelia-de-lange-syndrome/