In Cornelia de Lange syndrome (CdLS), various parts of the body are affected in the development of the skin, eyes, and joints. It is characterized by distinctive facial features, growth delays, intellectual disabilities, and limb abnormalities. Symptoms differ widely from individual to individual. CdLS is caused by mutations in the genes involved in gene expression regulation. CdLS cannot be cured, but treatments and interventions can improve people's quality of life.
There are seven genes involved in CdLS that have been identified so far: NIPBL, SMC1A, SMC3, RAD21, HDAC8, ANKRD11, and BRD4. These genes encode proteins that form a complex called cohesin, which helps control the expression of other genes during development. Cohesin is also necessary for maintaining the structure and function of chromosomes. Mutations in these genes disrupt cohesin's normal function, causing abnormal gene expression and developmental problems.
As a result of a new mutation in the affected individual, CdLS is most commonly inherited from the parents. One copy of the mutated gene is enough to cause CdLS, which can be inherited autosomally or X-linked in some cases. Depending on the type of mutation and the gender of the affected parent, CdLS is more likely to be inherited by offspring.
The symptoms of CdLS vary widely among affected individuals, and can range from mild to severe. Some of the common symptoms include:
Distinctive facial features, such as a small head, a long and prominent upper lip, thin and downturned lips, low-set ears, arched eyebrows that may join across the nose, long eyelashes, and a low hairline.
Growth delays, both before and after birth. Affected individuals may have a low birth weight, a short stature, and a small head circumference.
Intellectual disability, ranging from mild to profound. Affected individuals may have learning difficulties, speech and language delays, behavioral problems, and autism spectrum disorder.
Limb abnormalities, such as small hands and feet, curved fifth fingers, webbing of certain fingers or toes, and missing or malformed forearms, hands, or fingers.
Other possible symptoms, such as heart defects, gastrointestinal problems, hearing loss, vision problems, seizures, skeletal abnormalities, hormonal imbalances, and increased risk of infections.
The diagnosis of CdLS is based on the clinical features and the family history of the affected individual. Symptoms and signs of CdLS can be identified by a physical examination, growth assessment, and developmental evaluation. Detecting mutations in one of the genes associated with CdLS can confirm the diagnosis. Genetic testing is not available for all genes, however, and some cases of CdLS may be caused by unknown genes. Therefore, a negative genetic test does not rule out CdLS.
There is no specific treatment or cure for CdLS, but various therapies and interventions can help manage its symptoms and complications. Treatment plans vary depending on the needs and preferences of the affected person and their family. Some possible treatments include:
Growth hormone therapy, to stimulate growth and development.
Surgery, to correct heart defects, gastrointestinal problems, limb abnormalities, or other malformations.
Medications, to treat seizures, hormonal imbalances, infections, or other conditions.
Physical therapy, occupational therapy, and speech therapy, to improve motor skills, daily living skills, and communication skills.
Special education, behavioral therapy, and social skills training, to enhance learning, cognition, and social interaction.
Counseling and support groups, to provide emotional and psychological support for the affected person and their family.
Because CdLS is caused by new mutations that occur randomly, there is no known way to prevent it. The risk of having a child with CdLS can be assessed through genetic counseling, which provides information and guidance for family planning. CdLS can also be detected early through prenatal testing and newborn screening and appropriate care and support can be provided.
