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Cornelia de Lange Syndrome

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Introduction

The Questions and Answers that follow aim to provide an introduction to Cornelia de Lange syndrome (CdLS) for parents and other family members. Following those, we offer links to selected resources for more information and support and a list of valuable services.
More information about many topics relevant to children with CdLS and many other chronic conditions and their families can be found in the left menu. Detailed information aimed at primary care doctors can be found in our Cornelia de Lange Syndrome module.

What is Cornelia de Lange syndrome (CdLS) and what causes it?

CdLS is a congenital syndrome, meaning it is present from birth. Most of the signs and symptoms may be recognized at birth or shortly thereafter, although sometimes it may take many years. A child need not demonstrate each and every sign or symptom for the diagnosis to be made. Individuals with CdLS strongly resemble one another. Common characteristics include: low birth weight (usually, but not always, under 5 pounds), delayed growth and small stature, and small head size (microcephaly). Typical facial features include thin eyebrows which frequently meet at midline (synophrys), long eyelashes, short upturned nose, and thin, downturned lips. Other frequent findings include excessive body hair (hirsutism), small hands and feet, partial joining of the second and third toes, incurved 5th fingers, gastroesophageal reflux, seizures, heart defects, cleft palate, bowel abnormalities, feeding difficulties, and developmental delay. Limb differences, including missing limbs or portions of limbs, usually fingers, hands or forearms, are also found in some individuals. Four separate genes, NIPBL, SMC1A, SMC3, HDAC8 and likely as yet other unidentified genes, cause CdLS. Usually the gene changes sporadically in individuals with CdLS; their parents do not show signs of the syndrome.

What are the symptoms of CdLS?

Children with CdLS are usually small at birth, have a facial resemblance to other children with CdLS, have small or different hands and feet, and have some degree of intellectual disability.

How is it diagnosed?

The diagnosis of CdLS is made clinically, usually by a geneticist, who will examine your child to determine if signs and symptoms of the syndrome are present. Genetic testing is sometimes performed to confirm the diagnosis but, as a significant percentage of children with CdLS have a negative gene test, only a positive test is confirmatory.

What is the prognosis?

Most children with CdLS will live well into adulthood; however, each child must be evaluated 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 mild to moderate range. You should expect that a child with CdLS will have developmental delays.

What is the risk for other family members or future babies?

We think that the syndrome is caused by just 1 faulty gene. Every cell in our bodies contains about 50,000 genes. We each have 2 copies of each of these genes, 1 we inherit from our mother and the other from our father. In many cases we only need 1 good copy of the gene and 1 faulty copy is then 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, we think that 1 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 2 children with the syndrome. We are therefore more than 99% sure it will not happen again in your family. We think that in these cases a fault occurred early on in the development of the ovary or the testis and that instead of just 1 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 the syndrome they feel very unlucky, especially if it is their first child, and often believe that things will go wrong again if they have another child.

What treatments/therapies/medications are recommended or available?

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.

How will my child and our family be impacted?

The impact on your child and family will depend on how severely affected your child is but even children with “mild” CdLS require therapies and medical treatment not usually needed by typically developing children. They will also require special education help through school.

My pediatrician wants to schedule my child for a Nissen fundoplication and gastrostomy tube placement for tube feedings. I still want to try to teach my child to eat by mouth. What should I do?

Even after fundoplication and gastrostomy tube (G-tube) placement, children can be fed orally, as long as aspiration 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.

My child has episodes of crying and I can’t get her to stop. What can I do?

First, ask your pediatrician to evaluate your daughter to rule out obvious physical problems, such as ear infections, dental caries, 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.

My daughter used to sleep well, but over the last few months has started awakening many times during the night. She doesn’t seem to be in pain, but won’t go back to sleep.

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

How severe is my child compared to all of the other children?

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

How can I provide my child with better communication?

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

What is the likely cause of my child’s aggressive, self-injurious, or frustrated behaviors?

There can be many behavioral issues in CdLS and we do not understand the inherent causes. Often difficulty in communication can precipitate frustrated behaviors, and we always recommend augmented communication 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.

How can we manage self-injurious or aggressive behaviors in CdLS?

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.

Resources

Information & Support

Where can I go for further information?

For Parents and Patients

Support

Support (CdLS Foundation)

General

Cornelia de Lange Syndrome (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; U.S. National Library of Medicine.

Genetic Testing (CdLS Foundation)
A list of facilities that offer genetic testing for CdLS.

Services for Patients & Families in Montana (MT)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Studies

Research Studies in CdLS (CdLS Foundation)

Authors & Reviewers

Initial publication: March 2012; last update/revision: August 2019
Current Authors and Reviewers:
Author: Lynne M. Kerr, MD, PhD
Reviewer: Antonie Kline, MD
Funding: The Medical Home Portal thanks the 2011-2012 URLEND Medical Home Portal trainees group for their contribution to this page.

Page Bibliography

Kline AD, Krantz ID, Sommer A, Kliewer M, Jackson LG, FitzPatrick DR, Levin AV, Selicorni A.
Cornelia de Lange syndrome: clinical review, diagnostic and scoring systems, and anticipatory guidance.
Am J Med Genet A. 2007;143A(12):1287-96. PubMed abstract