Cornelia de lange syndrome

Cornelia de Lange Syndrome
Classification and external resources
ICD-10 9 OMIM DiseasesDB eMedicine MeSH C10.597.606.643.210

Cornelia de Lange Syndrome (CdLS) is a genetic disorder present from birth, but not always diagnosed at birth. It causes a range of physical, cognitive and medical challenges and affects both genders equally.

It is often termed as Bushy Syndrome and is also known as Amsterdam dwarfism. It is a genetic disorder that can lead to severe developmental anomalies. It affects the physical and intellectual development of a child. Exact incidence is unknown, but it is estimated at 1 in 10,000 to 30,000.[1]


The vast majority of cases are due to spontaneous genetic mutations.

It can be associated with mutations affecting the cohesin complex.[2]

Multiple genes have been associated with the condition. In 2004, researchers at the Children's Hospital of Philadelphia and the University of Newcastle upon Tyne (England), identified a gene (NIPBL) on chromosome 5 that causes CdLS when it is mutated. Since then, additional genes have been found (SMC1A, SMC3 and HDAC8) that cause CdLS when changed. There are likely other genes as well. Researchers hope to gain a better understanding of why CdLS varies so widely from one individual to another and what can be done to improve the quality of life for people with the syndrome. (For more information visit:

Name OMIM Gene Appx. % Notes
CDLS1 122470 NIPBL 50% A gene responsible for CdLS on Chromosome 5 was discovered in 2004 jointly by researchers at the Children's Hospital of Philadelphia, USA[3] and researchers at Newcastle University, UK.[4]
CDLS2 300590 SMC1A 5% In 2006, a second gene, on the X chromosome, was found by Italian scientists.
CDLS3 610759 SMC3 1% A third gene discovery was announced in 2007. The gene is on chromosome 10 and was also discovered by the research team in Philadelphia.

The latter two genes seem to correlate with a milder form of the syndrome.

In July 2012, the fourth “CdLS gene”—HDAC8—was announced. Many parents and professionals have questions about this latest finding and what it means. HDAC8 is an X-linked gene, meaning it is located on the X chromosome. Individuals with CdLS who have the gene change in HDAC8 make up just a small portion of all people with CdLS.[5]

Evidence of a linkage at chromosome 3q26.3 is mixed.[6]


The first ever documented case was in 1916 by Winfried Robert Clemens Brachmann[7] followed up by Cornelia Catharina de Lange,[8] a Dutch pediatrician, in 1933 after whom the disorder has been named.[9]


The diagnosis of CdLS is primarily a clinical one based on signs and symptoms (see below) observed through an evaluation by a physician, including a medical history, physical examination, and laboratory tests. Since 2006, testing for NIPBL and SMC1A has been available through the University of Chicago.[1] This is best accomplished through a referral to a genetics specialist or clinic.

CdLS is thought to be underdiagnosed and frequently misdiagnosed.

For more information on diagnosis, visit the CdLS Foundation's (U.S.) Web page, Here you can find Frequently Asked Questions as well as a Diagnostic Checklist for medical professionals to utilize in the diagnostic process.

Genetic testing for CdLS is offered through the following facilities:

Children's Hospital of Philadelphia[10]

(Research Lab currently providing testing to individuals whose previous blood test(s) didn't show changes in NIPBL or SMC1A, and for families with multiple cases of CdLS)

University of Chicago Genetic Services Laboratories[11]

(Clinical Lab)

Features and characteristics

Following are the features and characteristics that help in spotting this disorder: [12]

Children with this syndrome are often found to have long eyelashes, bushy eyebrows and synophrys (joined eyebrows). Body hair can be excessive and affected individuals are often shorter than their immediate family members.

CdLS can give rise to its own array of complexities. Children with CdLS often suffer from gastrointestinal tract difficulties, particularly gastroesophageal reflux. Vomiting, intermittent poor appetite, constipation, diarrhea or gaseous distention are known to be a regularity in cases where the GE tract problems are acute. Symptoms may range from mild to severe.

CdLS may include behavior problems, including self-stimulation, aggression, self-injury or strong preference to a structured routine. Many children with CdLS exhibit autistic-like behaviors.

Behavior problems in CdLS are not inevitable. Many behavior issues associated with CdLS are reactive (i.e., something happens within the person's body or environment to bring on the behavior) and cyclical (comes and goes). Often, an underlying medical issue causes a change in behavior. Once the medical issue is treated, the behavior diminishes.


[13] Often, an interdisciplinary approach to therapy and treatment of any medical issues that arise is recommended. A team for promotion of the child's well-being often includes speech, occupational and physical therapists, teachers, physicians and, most importantly, the parent(s).

Treatment protocols and guidelines, development skills charts and growth charts for males and females can be downloaded at


The Cornelia de Lange Syndrome (CdLS) Foundation[2].


External links

  • Cornelia de Lange Syndrome Foundation, Inc.
  • Children's Hospital of Philadelphia, The Center for Cornelia de Lange Syndrome and Related Diagnoses
  • The University of Chicago Genetic Services Laboratory
  • Development of Diagnostics and Therapeutics for Cornelia de Lange Syndrome
  • Genetic Alliance
  • Cleft and Craniofacial Anomalies
  • Pediatric Database (PEDBASE)
  • GeneReviews/NCBI/UW/NIH entry on Cornelia de Lange syndrome
  • Leiden Open Variation Database for Cornelia de Lange Syndrome

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