Char syndrome

Reviewed June 2008

What is Char syndrome?

Char syndrome is a condition that affects the development of the face, heart, and limbs. It is characterized by a combination of three major features: a distinctive facial appearance, a heart defect called patent ductus arteriosus, and hand abnormalities.

Most people with Char syndrome have a characteristic facial appearance that includes flattened cheek bones and a flat nasal bridge (the area of the nose between the eyes). The tip of the nose is also flat and broad. The eyes are wide-set with droopy eyelids (ptosis) and outside corners that point downward (down-slanting palpebral fissures). Additional facial differences include a shortened distance between the nose and upper lip (a short philtrum), a triangular-shaped mouth, and thick, prominent lips.

Patent ductus arteriosus is a common heart defect in newborns, and it occurs in most babies with Char syndrome. Before birth, the ductus arteriosus forms a connection between two major arteries (the aorta and the pulmonary artery). This connection normally closes shortly after birth, but it remains open in babies with patent ductus arteriosus. If untreated, this heart defect causes infants to breathe rapidly, feed poorly, and gain weight slowly. In severe cases, it can lead to heart failure. People with patent ductus arteriosus also have an increased risk of infection.

Hand abnormalities are another feature of Char syndrome. In most people with this condition, the middle section of the fifth (pinky) finger is shortened or absent. Other abnormalities of the hands and feet have been reported but are less common.

How common is Char syndrome?

Char syndrome is rare, although its exact incidence is unknown. Only a few families with this condition have been identified worldwide.

What genes are related to Char syndrome?

Mutations in the TFAP2B gene cause Char syndrome. This gene provides instructions for making a protein known as transcription factor AP-2β. A transcription factor is a protein that attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Transcription factor AP-2β regulates genes that are involved in development before birth. In particular, this protein appears to play a role in the normal formation of structures in the face, heart, and limbs.

TFAP2B mutations alter the structure of transcription factor AP-2β. Some of these mutations prevent the protein from binding to DNA, while other mutations render it unable to regulate the activity of other genes. A loss of this protein's function disrupts the normal development of several parts of the body before birth, resulting in the major features of Char syndrome.

Related Gene(s)

Changes in this gene are associated with Char syndrome.

TFAP2B

How do people inherit Char syndrome?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of Char syndrome?

These resources address the diagnosis or management of Char syndrome and may include treatment providers.

Gene Review: Char Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1106/)
Genetic Testing Registry: Char syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1868570)
MedlinePlus Encyclopedia: Patent Ductus Arteriosus (http://www.nlm.nih.gov/medlineplus/ency/article/001560.htm)

You might also find information on the diagnosis or management of Char syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/char-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/char-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Char syndrome?

You may find the following resources about Char syndrome helpful. These materials are written for the general public.

MedlinePlus - Health information
- Encyclopedia: Patent Ductus Arteriosus (http://www.nlm.nih.gov/medlineplus/ency/article/001560.htm)
- Health Topic: Congenital Heart Defects (http://www.nlm.nih.gov/medlineplus/congenitalheartdefects.html)
Additional NIH Resources - National Institutes of Health
National Heart, Lung, and Blood Institute: Patent Ductus Arteriosus (http://www.nhlbi.nih.gov/health/health-topics/topics/pda/)
Educational resources - Information pages
- American Heart Association: Patent Ductus Arteriosus (http://www.heart.org/HEARTORG/Conditions/CongenitalHeartDefects/AboutCongenitalHeartDefects/Patent-Ductus-Arteriosis-PDA_UCM_307032_Article.jsp)
- Cleveland Clinic Center for Consumer Health Information: Patent Ductus Arteriosus (http://my.clevelandclinic.org/childrens-hospital/health-info/diseases-conditions/heart/hic-Patent-Ductus-Arteriosus.aspx)
- Madisons Foundation (http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=400)
- Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=46627)
Patient support - For patients and families
- Children's Heart Foundation (http://childrensheartfoundation.org/)
- Congenital Heart Information Network (http://tchin.org/)
- Family Village: Heart Disorders and Defects (http://www.familyvillage.wisc.edu/lib_hart.html)
- Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/conghart.html)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1106/)
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Char syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1868570)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Char%20syndrome%5BTIAB%5D)%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/169100)

What other names do people use for Char syndrome?

Patent ductus arteriosus with facial dysmorphism and abnormal fifth digits

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Char syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Char syndrome?

aorta ; arteries ; artery ; autosomal ; autosomal dominant ; cell ; DNA ; gene ; heart failure ; incidence ; infection ; mutation ; philtrum ; protein ; ptosis ; pulmonary ; pulmonary artery ; syndrome ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

Gene Review: Char Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1106/)
Mani A, Radhakrishnan J, Farhi A, Carew KS, Warnes CA, Nelson-Williams C, Day RW, Pober B, State MW, Lifton RP. Syndromic patent ductus arteriosus: evidence for haploinsufficient TFAP2B mutations and identification of a linked sleep disorder. Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2975-9. Epub 2005 Jan 31. (http://www.ncbi.nlm.nih.gov/pubmed/15684060?dopt=Abstract)
Satoda M, Pierpont ME, Diaz GA, Bornemeier RA, Gelb BD. Char syndrome, an inherited disorder with patent ductus arteriosus, maps to chromosome 6p12-p21. Circulation. 1999 Jun 15;99(23):3036-42. (http://www.ncbi.nlm.nih.gov/pubmed/10368122?dopt=Abstract)
Satoda M, Zhao F, Diaz GA, Burn J, Goodship J, Davidson HR, Pierpont ME, Gelb BD. Mutations in TFAP2B cause Char syndrome, a familial form of patent ductus arteriosus. Nat Genet. 2000 May;25(1):42-6. (http://www.ncbi.nlm.nih.gov/pubmed/10802654?dopt=Abstract)
Slavotinek A, Clayton-Smith J, Super M. Familial patent ductus arteriosus: a further case of CHAR syndrome. Am J Med Genet. 1997 Aug 8;71(2):229-32. (http://www.ncbi.nlm.nih.gov/pubmed/9217229?dopt=Abstract)
Sweeney E, Fryer A, Walters M. Char syndrome: a new family and review of the literature emphasising the presence of symphalangism and the variable phenotype. Clin Dysmorphol. 2000 Jul;9(3):177-82. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10955477?dopt=Abstract)
Zannolli R, Mostardini R, Matera M, Pucci L, Gelb BD, Morgese G. Char syndrome: an additional family with polythelia, a new finding. Am J Med Genet. 2000 Nov 27;95(3):201-3. (http://www.ncbi.nlm.nih.gov/pubmed/11102923?dopt=Abstract)
Zhao F, Weismann CG, Satoda M, Pierpont ME, Sweeney E, Thompson EM, Gelb BD. Novel TFAP2B mutations that cause Char syndrome provide a genotype-phenotype correlation. Am J Hum Genet. 2001 Oct;69(4):695-703. Epub 2001 Aug 14. (http://www.ncbi.nlm.nih.gov/pubmed/11505339?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.