Answers to questions families often have about caring for their child with Cornelia de Lange syndrome

CdLS is a congenital syndrome, meaning it is there from birth. It causes intellectual disability and physical abnormalities. Most of the signs and symptoms may be recognized at birth or shortly after, though sometimes it may take many years. A child need not show all signs or symptoms for the diagnosis to be made. A diagnosis could be made through genetic testing or a clinical exam.

Mutations or changes in four separate genes, NIPBL, SMC1A, SMC3, HDAC8 and likely other genes that have not yet been identified, cause CdLS. Usually the gene changes sporadically in people with CdLS; their parents do not show signs of the syndrome.

Children with CdLS are usually small at birth (often weighing less than 5 pounds), with delayed growth, small stature, and small head size (microcephaly). Typical facial features include:

• thin eyebrows which frequently meet at midline (synophrys)
• long eyelashes
• short upturned nose
• thin, downturned lips

Other frequent findings include:

• excessive body hair (hirsutism)
• small hands and feet
• partial joining of the second and third toes
• incurved fifth fingers
• gastroesophageal reflux
• seizures
• heart defects
• cleft palate
• bowel abnormalities
• feeding difficulties (some children may need a feeding tube)
• developmental delay
• hearing loss (some children may need hearing aids)
• vision difficulties (some children may need glasses)

Limb differences, including missing limbs or portions of limbs, usually fingers, hands or forearms, are also found in some people. Some children may speech difficulties, including apraxia, or may be non-verbal when severely affected. People with CdLS strongly resemble one another.

The diagnosis of CdLS is usually made by a geneticist, who will examine your child to determine if signs and symptoms of the syndrome are present. Genetic testing is sometimes performed but the test is negative in 20-25% children with the condition. This may occur because some gene mutations that cause CdLS are not yet known (and thus not tested for) or an affected child has mosaicism for the gene where only some cells in the body are affected.

Most children with CdLS will live well into adult age; however, each child must be tested for life-threatening conditions such as heart defects, untreated gastroesophageal reflux, and bowel abnormalities. Most children with CdLS will have intellectual disability ranging from mild to profound; most fall in the moderate to severe range. You should expect that a child with CdLS will have developmental delays.

It is thought that the syndrome is caused by just one faulty gene. Every cell in the body contains about 50,000 genes. We each have two copies of each of these genes, one we inherit from our mother and the other from our father. In many cases we only need one good copy of the gene; in these cases, one faulty copy is not a problem. However, this is not always the case and for other genes, we need both copies of the gene to be working correctly. In CdLS, it is thought that one copy of a very important gene has a fault in it and that the fault occurs in either the egg or the sperm.

The chances of having another child with the syndrome are very small. There are only a few known cases in the world of a couple having two children with the syndrome. There is a 99% likelihood it will not happen again in your family. It is thought that in these cases a fault occurred early on in the development of the ovary or the testis and that instead of just one copy of an egg or sperm carrying the faulty gene, there were in fact several eggs or sperm with the fault. Even though couples know that it is extremely unlikely that they will have another child with CdLS they may still worry about it, especially if it is their first child.

Treatment is specific to each child and involves diagnostic testing to find out how CdLS is affecting the child’s health. Comprehensive evaluation helps your child’s doctor to understand how the syndrome is manifesting for your child, create a plan for addressing medical complications of CdLS, and treat other symptoms. Early Intervention Part C Program and other developmental therapies are very important and help maximize function in children with CdLS. Speech therapy is especially important.

The impact on your child and family will depend on how severely affected your child is, but even children with “mild” CdLS need therapies and medical treatment not usually needed by typically developing children. They will also require special education help through school. People with mild CdLS may need long-term support with activities of daily living (ADL) into adulthood.

Severe CdLS may mean major changes for a family. More severely affected children will likely require more supportive therapies and may need a full-time caregiver, even as an adult.

Even after fundoplication and gastrostomy tube (G-tube) placement, children can be fed orally, as long as aspiration (choking) isn’t a risk. In children who take enough calories orally, the G-tube can be used to relieve air buildup in the stomach. For children who take enough calories orally but have a difficult time getting enough liquids, parents may use the tube to supplement liquid intake. In children who aren’t eating enough, using a G-tube can ensure adequate nutrition while the child is learning to eat. The family can decrease tube feedings as oral intake increases. Gastrostomy tubes can be removed when they are no longer needed, usually after it has not been needed for several months. The hole in the abdomen usually seals shut within a few days of G-tube removal.

First, ask your pediatrician to evaluate your daughter to rule out obvious physical problems, such as ear infections, dental caries (cavities), sinusitis, and gastroesophageal reflux. If medical conditions are ruled out, your provider might focus on other approaches, such as a behavioral program or behavioral evaluation, and possibly medication.

Behavioral problems like episodes of crying may happen when children are non-verbal and cannot express themselves, and it is important to help children with communication (see "How can I provide my child with better communication?" below).

First, make sure there is no medical condition, such as dental caries (cavities), esophagitis from gastroesophageal reflux, or constipation, that is causing the frequent awakenings. If none are found, your primary care doctor may refer your child for a sleep evaluation and/or test for ferritin and iron levels (iron deficiency may cause restless leg syndrome). Your primary care doctor or sleep specialist will work with you on behavioral approaches and/or medications.

Severity depends on many factors. Physical severity is usually obvious at birth, and there can be more intellectual severity when more organ system involvement is present. Intellectual severity can be difficult to check until language comes in, which is often delayed in CdLS. There is a publication of severity scoring which can be helpful: [Kline: 2007].

In CdLS, verbal communication is delayed more than expressive language. Speech therapy should be started as soon as available. Sign language is recommended as soon as possible. Communication devices, such as computers, tablets, or picture exchange systems can be very helpful.

There can be many behavioral issues in CdLS and the underlying causes are not well understood. Difficulty in communication can often cause frustrated behaviors, and assisted or alternative communication is recommended to help prevent this. It is important to rule out organic causes of hidden pain, such as toothaches, sinus infections, gastroesophageal reflux disease, constipation or musculoskeletal pain, all of which can cause behavioral problems.

If available, evaluation with behavioral psychology, behaviorist, and/or child psychiatry can be helpful to assess the overall child. Behavioral modification can help greatly when addressing a specific negative behavior. Medications can be useful in managing psychiatric disturbances such as ADHD, anxiety, depression and aggressive tendencies.