Cornelia de Lange syndrome

Cornelia de Lange syndrome (CdLS), also known as Brachmann-de Lange syndrome, is a rare multisystem developmental disorder characterized by distinctive facial features, growth retardation, limb anomalies, and intellectual disability. The condition is present from birth and affects multiple organ systems. Characteristic facial features include synophrys (confluent eyebrows), long eyelashes, a small upturned nose with anteverted nares, a thin downturned upper lip, and micrognathia (small jaw). Growth restriction typically begins prenatally and continues postnatally, resulting in short stature. Upper limb abnormalities range from subtle changes such as small hands and short fifth fingers to severe reduction defects including oligodactyly or absent forearms. Intellectual disability varies from mild to severe, and many individuals exhibit behavioral features including self-injurious behavior, autistic-like traits, and attention difficulties. CdLS affects the gastrointestinal system frequently, with gastroesophageal reflux disease (GERD) being particularly common and often severe. Congenital heart defects occur in approximately 25% of affected individuals. Hearing loss (both sensorineural and conductive), ophthalmologic abnormalities (including myopia and ptosis), genitourinary anomalies (particularly cryptorchidism in males), and seizures are also recognized features. Feeding difficulties are common in infancy and may require specialized intervention. CdLS is caused by pathogenic variants in genes encoding components of the cohesin complex, including NIPBL (the most commonly affected gene, accounting for approximately 60% of cases), SMC1A, SMC3, RAD21, BRD4, HDAC8, and ANKRD11. There is no cure for CdLS; management is supportive and multidisciplinary. Treatment focuses on addressing specific symptoms such as surgical correction of limb or cardiac anomalies, management of GERD (which may require fundoplication), hearing aids, speech and behavioral therapy, and educational support. Early intervention programs and regular developmental assessments are essential to optimize outcomes.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Cornelia de Lange syndrome