Cornelia de Lange Syndrome | Boston Children's Hospital (2024)

What are the symptoms of Cornelia de Lange syndrome?

Cornelia de Lange syndrome causes particular facial features, the slowing of body growth, cognitive issues, and other abnormalities. Symptoms may include:

• malformations of the hands and arms
• microcephaly
• seizures
• gastrointestinal problems such as gastroesophageal reflux (GERD)
• autism spectrum disorders
• underdevelopment of the sexual organs
• cleft palate
• heart defects
• failure of the testes to descend into the scrotum (cryptorchidism)
• high, arched eyebrows, or eyebrows that meet in the midline
• widely spaced teeth or eyes
• hearing loss
• excessive hair growth
• myopia
• dental abnormalities

In mild Cornelia de Lange syndrome cases, some of the symptoms above may be less serious or even absent.

What causes Cornelia de Lange syndrome?

Cornelia de Lange syndrome is genetic condition that is caused by mutations in at least five genes (NIPBL, RAD21, SMC3, HDAC8, and SMC1A). The severity of the condition can vary greatly depending on the type of mutation and which gene is affected. More than half of people with CdLS have mutations in the NIPBL gene. This is also associated with more severe disease.

Cornelia de Lange syndrome is rarely inherited. Rather, it usually happens sporadically, with no family history of the disease. This happens because of de novo, or new, mutations.

The HDAC8 and SMC1A genes are found on one of the sex chromosomes, specifically the X chromosome. Only one copy of the mutated gene is necessary to cause the disorder, and it affects both females and males. This differs from many other X-linked disorders, where males are mostly affected. The NIPBL, RAD21, and SMC3 genes are found on autosomes, or the non-sex chromosomes, and only one copy of the mutated gene is necessary to cause the disorder.

The five genes associated with CdLS produce proteins that are involved with development before birth. Specifically, the proteins are responsible for guiding the development of the face, limbs, and other parts the body.

How is Cornelia de Lange syndrome diagnosed?

To diagnose CdLS, your doctor will review your child’s medical history and perform a physical examination. Your doctor may also order genetic testing to test for the specific mutations in the five genes associated with CdLS (NIPBL, RAD21, SMC3, HDAC8, and SMC1A) and other genes of interest.

How is Cornelia de Lange syndrome treated?

Your child’s doctor may recommend treatments for gastrointestinal issues. Gastroesophageal reflux (GERD) occurs when stomach acid flows back into the esophagus. Treatment for GERD varies by age but can include medication to reduce stomach acid or make the stomach empty faster. Your doctor may also recommend surgery in more severe cases or if the intestines are twisted. If nutritional needs are not being met, your doctor may prescribe supplemental formula or an intervention to deliver nutrition directly into the stomach.

Your doctor may prescribe medications to treat seizures. Hearing loss may be treated with hearing aids or cochlear implants. Your doctor may also recommend surgery or other treatments for heart defects or to improve mobility of the hands, arms, legs, or feet.

Your child may also need physical therapy, speech therapy, or occupational therapy to improve development and long-term prognosis. Your doctor may also suggest alternative methods of communication, such as sign language, if your child’s verbal skills are lacking.

How we care for Cornelia de Lange syndrome

The Cornelia de Lange Syndrome and Related Disorders Clinic at Boston Children’s Hospital is dedicated to the comprehensive care of children and adolescents who have CdLS or related conditions known as cohesinopathies.