Cornelia de lange syndrome

Cornelia de Lange Syndrome

Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder that affects multiple parts of the body. It is characterized by distinctive facial features, growth delays, intellectual disability, and limb abnormalities. The syndrome is named after the Dutch pediatrician Cornelia de Lange, who first described it in 1933.

Clinical Features

Individuals with Cornelia de Lange Syndrome often present with a range of clinical features, which can vary in severity. Common characteristics include:

• Facial Features: Distinctive facial features such as arched eyebrows that often meet in the middle (synophrys), long eyelashes, a small upturned nose, and thin downturned lips.
• Growth Delays: Prenatal and postnatal growth retardation, leading to short stature.
• Limb Abnormalities: Upper limb defects, which can range from small hands to missing fingers or forearms.
• Intellectual Disability: Varying degrees of intellectual disability, from mild to severe.
• Behavioral Issues: Some individuals may exhibit autistic-like behaviors, including self-injury and repetitive movements.
• Other Health Issues: Gastroesophageal reflux, hearing loss, and heart defects are also common.

Genetics

Cornelia de Lange Syndrome is primarily caused by mutations in the NIPBL gene, which is responsible for the majority of cases. Other genes associated with CdLS include SMC1A, SMC3, RAD21, and HDAC8. These genes are involved in the cohesin complex, which plays a crucial role in chromosome segregation during cell division and in regulating gene expression.

CdLS is usually inherited in an autosomal dominant manner, meaning a single copy of the altered gene in each cell is sufficient to cause the disorder. However, most cases result from new (de novo) mutations and occur in people with no history of the disorder in their family.

Diagnosis

Diagnosis of Cornelia de Lange Syndrome is based on clinical evaluation and the identification of characteristic features. Genetic testing can confirm the diagnosis by identifying mutations in the associated genes. Early diagnosis is important for managing the symptoms and improving the quality of life for affected individuals.

Management

There is no cure for Cornelia de Lange Syndrome, and treatment focuses on managing the symptoms and complications. This may involve:

• Multidisciplinary Care: Involving specialists such as pediatricians, cardiologists, gastroenterologists, and developmental therapists.
• Educational Support: Special education programs tailored to the individual's needs.
• Surgical Interventions: For limb abnormalities or other physical defects.
• Therapies: Physical, occupational, and speech therapy to address developmental delays and improve communication skills.

Epidemiology

Cornelia de Lange Syndrome is estimated to occur in 1 in 10,000 to 30,000 live births. It affects both males and females equally and has been reported in various ethnic groups worldwide.

Research and Future Directions

Ongoing research aims to better understand the genetic and molecular mechanisms underlying Cornelia de Lange Syndrome. Advances in genetic testing and molecular biology may lead to improved diagnostic methods and potential therapeutic targets in the future.

Also see

• Genetic Disorders
• Cohesin Complex
• Intellectual Disability
• Autosomal Dominant Inheritance

NIH genetic and rare disease info

• NIH info on Cornelia de lange syndrome

Cornelia de lange syndrome is a rare disease.