Cornelia de Lange Syndrome
|Cornelia de Lange Syndrome|
|Classification and external resources|
|ICD-10||Q87.1 (ILDS Q87.170)|
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.
The vast majority of cases are due to spontaneous genetic mutations.
Multiple genes have been associated with the condition. In 2004, researchers at the Children's Hospital of Philadelphia (United States) 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: http://www.cdlsusa.org/research/genetic-information.htm)
|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 and researchers at Newcastle University, UK.|
|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.
Evidence of a linkage at chromosome 3q26.3 is mixed.
The first ever documented case was in 1916 by Winfried Robert Clemens Brachmann followed up by Cornelia Catharina de Lange, a Dutch pediatrician, in 1933 after whom the disorder has been named.
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. 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, http://www.cdlsusa.org/what-is-cdls/diagnosis-of-cdls.htm. 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
(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
Features and characteristics
|This section does not cite any references or sources. (July 2011)|
Following are the features and characteristics that help in spotting this disorder: 
- Low birth weight (usually under 5 pounds/2.5 kilograms)
- Delayed growth and small stature
- Developmental delay
- Limb differences (missing limbs or portions of limbs)
- Small head size (microcephaly)
- Thick eyebrows, which typically meet at midline (synophrys)
- Long eyelashes
- Short upturned nose and thin downturned lips
- Long philtrum
- Excessive body hair
- Small hands and feet
- Small widely spaced teeth
- Low-set ears
- Hearing impairments
- Vision abnormalities (e.g., ptosis, nystagmus, high myopia, hypertropia)
- Partial joining of the second and third toes
- Incurved 5th fingers
- Gastroesophageal reflux
- Heart defects
- Cleft palate
- Feeding problems
- Hypoplastic genitalia
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.
 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).
The Cornelia de Lange Syndrome (CdLS) Foundation is a nonprofit, family support organization based in Zerahu, Connecticut, that exists to ensure early and accurate diagnosis of CdLS, promote research into the causes and manifestations of the syndrome, and help people with a diagnosis of CdLS, and others with similar characteristics, make informed decisions throughout their lives. The current medical director is Dr. Tonie Kline. In addition to Reaching Out, a quarterly newsletter, the Foundation produces and distributes other publications on CdLS, as well as an awareness video and materials for professionals .
- "Bushy Syndrome- Genetics Home Reference". Retrieved 2007-08-24.
- Liu J, Krantz ID (October 2009). "Bushy Syndrome, cohesin, and beyond". Clin. Genet. 76 (4): 303–14. doi:10.1111/j.1399-0004.2009.01271.x. PMC 2853897. PMID 19793304.
- Krantz ID, McCallum J, DeScipio C, et al. (2004). "Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B". Nature Genetics 36 (6): 631–5. doi:10.1038/ng1364. PMID 15146186.
- Tonkin E, Wang TJ, Lisgo S, Bamshad MJ, Strachan T (2004). "NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome". Nature Genetics 36 (6): 636–641. doi:10.1038/ng1363. PMID 15146185.
- "HDAC8 FAQ Sheet". CdLS Foundation Web site. Cornelia de Lange Syndrome Foundation. Retrieved 12 February 2013.
- Krantz ID, Tonkin E, Smith M, et al. (June 2001). "Exclusion of linkage to the CDL1 gene region on chromosome 3q26.3 in some familial cases of Cornelia de Lange syndrome". American Journal of Medical Genetics 101 (2): 120–9. doi:10.1002/1096-8628(20010615)101:2<120::AID-AJMG1319>3.0.CO;2-G. PMID 11391654.
- Brachmann, W. Ein Fall von symmetrischer Monodaktylie durch Ulnadefekt, mit symmetrischer Flughautbildung in den Ellenbeugen, sowie anderen Abnormitaeten (Zwerghaftigkeit, Halsrippen, Behaarung) (A case of symmetrical monodactyly, representing ulnar deficiency, with symmetrical antecubital webbing and other abnormalities, (dwarfism, cervical ribs, hirsutism)). Jahrbuch fuer Kinderheilkunde und physische Erziehung 84: 225-235, 1916.
- de Lange, C. Sur un type nouveau de degenerescence (typus Amstelodamensis). Arch. Med. Enfants 36: 713-719, 1933.
- "Children's Hospital of Philadelphia". Children's Hospital of Philadelphia. Retrieved 12 February 2013.
- "The University of Chicago Genetic Services Laboratory". The University of Chicago Genetic Services Laboratory. Retrieved 12 February 2013.
- "CdLS Foundation - Characteristics of CdLS". Cornelia de Lange Syndrome Foundation. Retrieved 12 February 2013.
- "CdLS Foundation - Treatment Protocols". 12 February 2013. Retrieved 12 February 2013.
- "Cornelia de Lange Syndrome Foundation". 2013. Retrieved 12 February 2013.
- 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