Cornelia de Lange syndrome (CdLS) is a pan-ethnic disorder characterized by pre- and postnatal growth retardation and various congenital anomalies, including a facial gestalt, limb anomalies, gastrointestinal disorders, hirsutism, and intellectual disability. Mild to severe forms of CdLS have been observed.
Approximately 37 to 47% of patients with CdLS have a mutation in the NIPBL gene identifiable by sequencing. Large deletions encompassing one or more exons of NIPBL have been identified in 5% of patients without mutations detectable by sequencing. The clinical course of patients with large deletions in the NIPBL gene, including growth and motor delay, is severe. NIPBL mutations are inherited in an autosomal dominant fashion.
SMC1A mutations have been observed in 5% of patients with CdLS and are composed mostly of missense and in-frame small deletions, and rarely of large in-frame deletions. Mutations in the SMC1A gene lead to mild to moderate phenotypes, including non-specific X-linked mental retardation. SMC1A mutations are X-linked; however, since SMC1A escapes inactivation, males and females with a mutation in SMC1A are affected.
Additionally, in 4-14% of patients with a clinical diagnosis of CdLS, a genomic deletion or duplication not including NIPBL or SMC1A was identified by karyotype or array CGH.