Cornelia de Lange Syndrome

Cornelia de Lange syndrome (CdLS) is a rare genetic disorder caused by dysregulation in transcriptional systems based on deficits in cohesin-related genes, with the phenotype presenting as a clinical spectrum of developmental and functional affected systems (Cornelia de Lange spectrum disorder). The genetic alteration results in abnormalities of multiple organ systems leading to somatic and functional changes affecting limb, gastrointestinal, endocrine, peripheral and central nervous systems, among others. The behavioral and psychiatric manifestations of CdLS were recognized in the 1970s as paradigmatic repetitive and self-injurious behaviors (SIB). The behavioral phenotype of CdLS includes autistic traits, but in contrast to classic autism spectrum disorder (ASD), the phenotype is characterized by anxiety, expressive communication deficits, and repetitive behaviors, including SIB. Brain imaging studies are scarce but point to various manifestations ranging from cerebral atrophy, white matter involvement, dilated ventricles, and in some cases, cerebellar hypoplasia and/or a striking lack of development or hypoplasia of cortical structures. Interfering repetitive behaviors include compulsions and ritualistic tendencies. Expressive communication deficits are prominent, while the use of gestures can be used as a compensatory strategy. An array of anxiety symptoms, with significant social anxiety, is another key feature in the behavioral phenotype of CdLS. In summary, the behavioral phenotype of CdLS points to a constellation of anxiety, repetitive behaviors including SIB, and expressive deficits. Self-injurious behaviors are often related to somatic pain. A multidisciplinary approach to the management of this complex condition is warranted to include somatic and behavioral/psychiatric approaches to therapeutics.