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Cornelia de Lange syndrome

What is Cornelia de Lange syndrome?

Cornelia de Lange syndrome (CdLS) is a developmental disorder characterized by slow growth before and after birth, which affects many parts of the body. The collection of symptoms comprising the syndrome were thought to be first described by Dutch pediatrician Dr. Cornelia de Lange in 1933. However, the condition is occasionally referred to as Brachmann-de Lange syndrome after Dr. W. Brachmann, who described similar symptoms in a patient in 1916. Signs of CdLS can include short stature, intellectual disability, limb defects, distinctive facial features, and behavior problems similar to autism. The disease is caused by mutations in at least five genes: NIPBL, SMC1A, HDAC8, RAD21 and SMC3. These genes produce structural and functional protein components of the cohesin complex which plays a key role in directing development before birth. There is no cure for the condition, but signs and symptoms may be treated according to each individual.

 

Synonyms

  • Brachman-de Lange Syndrome
  • Cornelia de Lange Syndrome

Cornelia de Lange syndrome (CdLS) is a developmental disorder characterized by slow growth before and after birth, which affects many parts of the body. The collection of symptoms comprising the syndrome were thought to be first described by Dutch pediatrician Dr. Cornelia de Lange in 1933. However, the condition is occasionally referred to as Brachmann-de Lange syndrome after Dr. W. Brachmann, who described similar symptoms in a patient in 1916. Signs of CdLS can include short stature, intellectual disability, limb defects, distinctive facial features, and behavior problems similar to autism. The disease is caused by mutations in at least five genes: NIPBL, SMC1A, HDAC8, RAD21 and SMC3. These genes produce structural and functional protein components of the cohesin complex which plays a key role in directing development before birth. There is no cure for the condition, but signs and symptoms may be treated according to each individual.

Acknowledgement of Cornelia de Lange syndrome has not been added yet.

The exact prevalence of CdLS is unknown but it likely affects 1 in 10,000 to 30,000 newborns. It is probable that CdLS is often underdiagnosed as those affected with mild or uncommon characteristics may never be recognized as having the condition. It affects both genders equally and occurs in individuals of all races and ethnic backgrounds.

Name Abbreviation
Brachman-de Lange Syndrome BdLS
Cornelia de Lange Syndrome CdLS

Most CdLS cases (approx. 60%) are caused by mutations in the NIPBL gene. Around 10% of individuals with CdLS have mutations in one of the four known genes SMC1A, SMC3, HDAC8 and RAD21. Researchers have identified other genes that when altered can also cause CdLS (ANKRD11 and BRD4). Many of the genes that are linked to CdLS encode proteins, which play a key role in human development before birth. When mutations in these genes exist, they can lead to an abnormal protein unable to carry out its normal function, affecting early development. In the remaining 30% of affected individuals, the underlying genetic cause of CdLS is unknown. 

While CdLS can be inherited in an autosomal dominant or X-linked manner*, most cases are the result of new (de novo) mutations and often occur in individuals with no family history of the condition.

*Autosomal dominant inheritance - when one copy of the altered gene in each cell is sufficient enough to cause the disease. 

X-linked dominant pattern of inheritance - The mutated gene that causes the disease is located on the X chromosome, one of the two sex chromosomes. In X-linked CdLS, one copy of the altered gene in each cell may be enough to cause the disease.

 

CdLS is highly variable with symptoms ranging from relatively mild to severe. However, affected individuals typically have distinctive craniofacial features, such as microcephaly (smaller head size than normal for her/his age), arched eyebrows that grow together in the middle, low-set ears, and widely spaced teeth. Around 80-99% of individuals with CdLS tend to have an abnormally low-pitched voice, anteverted nares (upturned nasal tip, nose and nostrils), absent ear canal, brachycephaly (short and broad skull), and curly eyelashes. Individuals with CdLS may experience one or more of the following: 

  • Delayed growth before and after birth, leading to smaller body and head size, skeletal system, smaller hands and feet as well as missing forearms and fingers

  • Autistic and/or self-destructive behaviors

  • Gastrointestinal problems

  • Hirsutism (excess hair growth)

  • Hearing loss

  • Myopia (nearsightedness)

  • Congenital heart defects

  • Genital abnormalities

  • Seizures

CdLS is typically diagnosed when certain symptoms and signs are present, such as head and face appearance (>95%), growth failure (>95%), intellectual disability (>95%), limb abnormalities (>95%), excess hair (in more than 80% of cases). As CdLS is so variable, many affected individuals have characteristic facial features but may not exhibit other symptoms like limb defects or intellectual disability. The diagnosis of CdLS is established with the presence of clinical features and/or by the genetic test that can indicate a variation in any of the genes associated with the disease.

Molecular genetic testing for mutations in the five genes associated with CdLS can be used to confirm the diagnosis and can be especially useful when physical features are mild or unusual. Prenatal diagnosis is also possible if a specific gene mutation in one of the aforementioned genes has been identified.

As CdLS can affect many different parts of the body and is so variable, treatment varies across individuals but may include:

  • Supplemental formulas and/or gastrostomy tube placement to address nutritional needs and improve growth delay

  • Support from physical, occupational and speech therapists

  • Surgery for any skeletal abnormalities, gastrointestinal issues, congenital heart defects, and any other health complications

  • Medications to prevent or manage seizures 

Individuals with CdLS can live relatively normal lives with most affected children living well into adulthood. However, depending on the severity of symptoms and features of the disease, such as abnormalities of the heart, life expectancy may decrease in those affected. 

 

Tips or Suggestions of Cornelia de Lange syndrome has not been added yet.

Cornelia de Lange Syndrome Foundation, Inc. Characteristics of CdLS. 2018. Available from: https://www.cdlsusa.org/characteristics-of-cdls/

National Center for Advancing Translational Sciences: Genetic and Rare Diseases Information. N.d. Cornelia De Lange Syndrome. Available from: https://ghr.nlm.nih.gov/condition/cornelia-de-lange-syndrome

National Organization for Rare Disorders. Cornelia De Lange Syndrome. 2020. Available from: https://rarediseases.org/rare-diseases/cornelia-de-lange-syndrome/

U.S. National Library of Medicine: Genetics Home Reference. 2020. Cornelia de Lange Syndrome. Available from: https://ghr.nlm.nih.gov/condition/cornelia-de-lange-syndrome#diagnosis

Community Details Update Created by RareshareTeam
Last updated 30 Sep 2020, 07:23 PM

Posted by RareshareTeam
30 Sep 2020, 07:23 PM

Hi everyone,

The Cornelia de Lange syndrome community details have been updated. We added more information about the cause, prevalence, symptoms, diagnosis, and treatment. Hopefully, you find it helpful. 

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Army major walking barefoot from Cornwall to Edinburgh to fund treatment for daughter with rare disease 07/11/2020
Barefoot major finishes 700 mile walk for daughter 08/15/2020
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I have a 3 month old grand niece with cdls and want to keep informed.

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Created by RareshareTeam | Last updated 30 Sep 2020, 07:23 PM


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