An Overview of Cornelia de Lange Syndrome

Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that causes distinctive facial features, growth delays, limb malformations, behavioral problems, and a variety of other symptoms. The condition can range from mild to severe and affect multiple parts of the body. It was named after Dutch pediatrician Cornelia de Lange, who first described the condition in two children in 1933.

CdLS is estimated to affect between one in 10,000 and one in 30,000 newborns. The exact number of cases isn't known since mild cases may go undiagnosed. 

Symptoms

Symptoms of Cornelia de Lange syndrome can often be recognized at birth. People with CdLS have specific facial features such as:

• Arched, thick eyebrows that usually meet in the middle
• Long eyelashes
• Low front and back hairlines
• A short, upturned nose
• Downturned angles of the mouth and thin upper lip
• Low-set and malformed ears
• Cleft palate

Other abnormalities, which may or may not be present at birth, include: 

• Very small head (microcephaly)
• Growth delays
• Eye and vision problems
• Hearing loss
• Excessive body hair, which may thin as the child grows
• Short neck
• Hand abnormalities, such as missing fingers, very small hands, or inward deviation of the pinky fingers
• Intellectual disabilities
• Self-injury problems and aggressive behavior

Infants with the condition may have trouble feeding. Children with CdLS may also have gastroesophageal reflux disease (GERD, a digestive disorder in which stomach acid backs up into the esophagus) and dental problems.

Causes

Cornelia de Lange syndrome cases are usually caused by gene mutations. More than half of people with the condition have a mutation in the NIPBL gene.

The syndrome has also been linked to at least four other gene mutations, including SMC1A, HDAC8, RAD21, and SMC3. The proteins from these genes contribute to the structure of the cohesion complex, proteins that help guide development before a baby is born. A mutation can disrupt that development during the early stages.

Diagnosis

Cornelia de Lange syndrome may be diagnosed at different ages. It can sometimes be detected during an ultrasound of the fetus, which may show limb abnormalities, a cleft lip, growth delays, an abnormal facial profile, or other signs of CdLS.

CdLS is often recognized at birth, based on typical symptoms, including facial features, excessive hair, small size, and small hands or feet. Other conditions may point toward CdLS, including diaphragmatic hernia (hole in the muscle separating the chest and abdomen), kidney anomalies, and congenital heart disease (heart disease present at birth).

People with mild cases may be diagnosed later in childhood. Facial features may have some subtle signs of CdLS. Intellectual disabilities may become more apparent, and aggressive behavior, including self-harm, may also become an issue.

Once diagnosed with CdLS, a child may need to be evaluated for malformations that cause medical issues. These include routine echocardiography (ultrasound of the heart to check heart chambers and valves) and renal sonography (ultrasound of the kidneys), since 25% of people with CdLS have a cardiac abnormality and 10% have a kidney malformation.

Treatment

Treatment focuses on managing symptoms to help people with CdLS lead better lives. Infants benefit from early intervention programs for improving muscle tone, managing feeding problems, and developing fine motor skills. Supplemental formulas or gastrostomy tube placement can help improve any growth delays.

As a child grows, physical, occupational, and speech therapy can benefit those with challenges. Surgery may be needed for skeletal abnormalities or congenital heart problems.

Mental health professionals can help manage behavioral symptoms of the condition. Children may also need to see cardiologists for heart problems or ophthalmologists for eye problems.

A Word From Verywell

Cornelia de Lange syndrome affects different people in different ways, and signs and symptoms may differ from individual to individual. If your child is diagnosed, their physician will talk with you about a specific treatment plan and suggest any services and support groups to help with your child's needs.