Cornelia de Lange syndrome is an autosomal dominant genetic disorder that causes a variety of developmental defects. As with most genetic disorders, the severity of the signs and symptoms varies greatly among individuals with Cornelia de Lange syndrome. The disorder is characteristic of causing mental and physical developmentally delayed defects in young growing children. Although the exact prevalence rate is unknown, it is estimated that Cornelia de Lange syndrome affects 1 in roughly 10,000 to 30,000.
Signs and Symptoms
Cornelia de Lange syndrome has distinct symptoms that can include slow growth during development of a child during and after pregnancy, organ, facial and skeletal abnormalities, and delayed or decreased intelligence.
The dysmorphic features of an affected child are perhaps the most distinctive and consistent symptom of Cornelia de Lange syndrome. Individuals are found to have a short neck, arched eyebrows, short upturned nose and low-set ears. Some features of the mouth can be influenced as well; such has a thin upper lip, spaced teeth and a high or cleft palate.
Some individuals have small hands and feet in mild cases to more extremely reduced upper limbs in the more severe cases. This can include the presence of fewer than five digits on the hands or toes to the complete lack of a forearm in some patients. Many patients have a small stature that occurs prenatally. Also, the height, weight and the size of the head is disproportionate during development of a patient.
Additional symptoms of Cornelia de Lange syndrome include excessive body hair, called hirsutism, hearing loss and abnormalities of the digestive tract. Some behavior problems, such as autism, attention deficit disorder with or without hyperactivity, and depression might occur during the lifespan of a patient with Cornelia de Lange syndrome.
Cornelia de Lange syndrome diagnosis is based on dysmorphic features and full measure of intelligence. To be completely accurate, testing for mutations in the genes, NIPBL, SMC1A, and SMC3 occurs.
SMC1A/3 stands for “structural maintenance of chromosomes 1A/3”. The proteins made from these genes make a complex called cohesion that helps to regulate the organization and maintenance of chromosomes during cellular division. When cells divide, they replicate their DNA in each chromosome into two structures called sister chromatids. These chromatids are attached to one another held by the cohesion complex.
The NIPBL gene makes a protein called delangin that has an important role in human development. During pregnancy, the protein can be found in developing limbs, bones, the skull, and the spine. Another function of delangin is to help the splitting of chromosomes during cellular division, much like SMC1A and SMC3. It too makes a subunit responsible for the formation of the cohesion complex. Delangin controls the interaction of the cohesion and the DNA of the chromatids during division.
There is no known cure for Cornelia de Lange syndrome but there are therapies to help with the consequences of the disorder. These can include speech, occupational and physical therapist, teachers, parents, and community centers. Surgeries exist to help eliminate the abnormalities of the face and limbs. There is no known preventative during pregnancy that can stop the onset of Cornelia de Lange syndrome.