What is Cornelia de Lange syndrome?

Causes and Symptoms

Cornelia de Lange syndrome occurs at an estimated rate of 1 per 10,000 to 30,000 live births. Sometimes siblings have this syndrome, reinforcing the hypothesis that it is hereditary. Although the precise causation is unknown, researchers are investigating the possibility that mutations in the NIPBL, SMC1A, and SMC3 genes cause Cornelia de Lange syndrome.

Patients with this syndrome are smaller in size and weight than average infants, and their growth and motor development are usually delayed. Upper limbs are often deformed, with missing tissues. Although legs attain average size and development appropriate to patients’ age, sometimes toes are webbed. Hands tend to be small. Patients share similar facial characteristics. Heads are abnormally small with upturned nostrils and thin lips and eyebrows. Heavy body hair often grows.

Intellectual development is impeded, particularly affecting vocalization. Hearing and vision sometimes are affected. Patients often suffer heart abnormalities, cleft palate, reflux, and convulsions. They are vulnerable to infections because of impaired immune systems.

Prenatal ultrasounds can reveal if fetuses have physical deficiencies that might be associated with Cornelia de Lange syndrome. Physicians identify the syndrome by observing characteristics evident in infants and toddlers. Genetic professionals confirm diagnoses, especially in patients whose symptoms are less obvious.

Treatment and Therapy

Many newborns with Cornelia de Lange syndrome require incubation to monitor respiration and nutrition. Antibiotics and other medications, as well as surgical procedures, are administered to treat specific ailments affecting these individuals. Physical therapy, auditory devices, and prosthetics can aid children. Some patients have shortened life spans and are unable to live autonomously. Heart conditions cause most of the deaths associated with this syndrome.

Although no known cure or prevention exists, medical awareness and treatment of this syndrome can extend the life span and enhance the quality of life for many patients. Some patients with milder conditions survive to average life expectancies. Adults with this syndrome attain a height from four to five feet and undergo puberty at normal ages. Various therapies can assist patients who exhibit aggressive and self-destructive behaviors and improve communication and social skills.

Perspective and Prospects

In 1916, Winfried R. Brachmann became the first physician to document this syndrome’s characteristics in an infant. Dutch pediatrician Cornelia C. de Lange clinically described two patients in 1933 and discussed her work at neurological conferences. By the early twenty-first century, researchers had established a Cornelia de Lange syndrome database to coordinate information. Geneticists, particularly Ian Krantz and his colleagues at the University of Pennsylvania's Department of Genetics, conducted molecular investigations to determine the genetic causation of this syndrome. A mutation in a gene known as NIPBL is now known to be one cause of this relatively rare disorder. This gene provides directions for the making of a protein, delangin, which is very important in developmental regulation of a number of body parts in the fetus.

Bibliography:

"About CdLS." Cornelia de Lange Syndrome Foundation, 2010.

Benson, M. “Cornelia de Lange Syndrome: A Case Study.” Neonatal Network 21, no. 3 (April, 2002): 7–13.

Berg, J. M., et al. The De Lange Syndrome. New York: Pergamon Press, 1970.

Braunholz, Diana, et al. "Isolated NIBPL Missense Mutations That Cause Cornelia de Lange Syndrome Alter MAU2 Interaction." European Journal of Human Genetics 20, no. 3 (March, 2012): 271–276.

"Cornelia de Lange Syndrome." Genetics Home Reference, July 2012.

Gardner, R. J. M. “Another Explanation for Familial Cornelia de Lange Syndrome.” American Journal of Medical Genetics 118A, no. 2 (April 15, 2003): 198.

Gilbert, Patricia. Dictionary of Syndromes and Inherited Disorders. 3d ed. Chicago: Fitzroy Dearborn, 2000.