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Genetics Home Reference: your guide to understanding genetic conditions
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Clouston syndrome

Reviewed March 2014

What is Clouston syndrome?

Clouston syndrome is a form of ectodermal dysplasia, a group of about 150 conditions characterized by abnormal development of some or all of the ectodermal structures, which include the skin, hair, nails, teeth, and sweat glands. Specifically, Clouston syndrome is characterized by abnormalities of the hair, nails, and skin, with the teeth and sweat glands being unaffected.

In infants with Clouston syndrome, scalp hair is sparse, patchy, and lighter in color than the hair of other family members; it is also fragile and easily broken. By puberty, the hair problems may worsen until all the hair on the scalp is lost (total alopecia). The eyelashes, eyebrows, underarm (axillary) hair, and pubic hair are also sparse or absent.

Abnormal growth of fingernails and toenails (nail dystrophy) is also characteristic of Clouston syndrome. The nails may appear white in the first years of life. They grow slowly and gradually become thick and misshapen. In some people with Clouston syndrome, nail dystrophy is the most noticeable feature of the disorder.

Many people with Clouston syndrome have thick skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis); areas of the skin, especially over the joints, that are darker in color than the surrounding skin (hyperpigmentation); and widened and rounded tips of the fingers (clubbing).

How common is Clouston syndrome?

The prevalence of Clouston syndrome is unknown. Cases have been reported in many populations; the disorder is especially common among people of French-Canadian descent.

What genes are related to Clouston syndrome?

Clouston syndrome is caused by mutations in the GJB6 gene. This gene provides instructions for making a protein called gap junction beta 6, more commonly known as connexin 30. Connexin 30 is a member of the connexin protein family. Connexin proteins form channels called gap junctions, which permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells. The size of the gap junction and the types of particles that move through it are determined by the particular connexin proteins that make up the channel. Gap junctions made with connexin 30 transport potassium ions and certain small molecules.

Connexin 30 is found in several different tissues throughout the body, including the skin (especially on the palms of the hands and soles of the feet), hair follicles, and nail beds, and plays a role in the growth and development of these tissues.

GJB6 gene mutations that cause Clouston syndrome change single protein building blocks (amino acids) in the connexin 30 protein. Although the effects of these mutations are not fully understood, they lead to abnormalities in the growth, division, and maturation of cells in the hair follicles, nails, and skin.

Related Gene(s)

Changes in this gene are associated with Clouston syndrome.

  • GJB6

How do people inherit Clouston 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 most cases, an affected person inherits the mutation from one affected parent. Other cases 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 Clouston syndrome?

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

  • Gene Review: Hidrotic Ectodermal Dysplasia 2 (http://www.ncbi.nlm.nih.gov/books/NBK1200/)
  • Genetic Testing Registry: Hidrotic ectodermal dysplasia syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0162361)

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

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

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

What other names do people use for Clouston syndrome?

  • Clouston hidrotic ectodermal dysplasia
  • Clouston's syndrome
  • ECTD2
  • ectodermal dysplasia 2, Clouston type
  • HED2
  • hidrotic ectodermal dysplasia 2

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 Clouston syndrome?

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

What glossary definitions help with understanding Clouston syndrome?

acids ; alopecia ; autosomal ; autosomal dominant ; cell ; channel ; connexin ; dysplasia ; gap junctions ; gene ; inherited ; ions ; mutation ; potassium ; prevalence ; protein ; puberty ; syndrome

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

References

  • Baris HN, Zlotogorski A, Peretz-Amit G, Doviner V, Shohat M, Reznik-Wolf H, Pras E. A novel GJB6 missense mutation in hidrotic ectodermal dysplasia 2 (Clouston syndrome) broadens its genotypic basis. Br J Dermatol. 2008 Dec;159(6):1373-6. doi: 10.1111/j.1365-2133.2008.08796.x. Epub 2008 Aug 19. (http://www.ncbi.nlm.nih.gov/pubmed/18717672?dopt=Abstract)
  • Essenfelder GM, Bruzzone R, Lamartine J, Charollais A, Blanchet-Bardon C, Barbe MT, Meda P, Waksman G. Connexin30 mutations responsible for hidrotic ectodermal dysplasia cause abnormal hemichannel activity. Hum Mol Genet. 2004 Aug 15;13(16):1703-14. Epub 2004 Jun 22. (http://www.ncbi.nlm.nih.gov/pubmed/15213106?dopt=Abstract)
  • Fraser FC, Der Kaloustian VM. A man, a syndrome, a gene: Clouston's hidrotic ectodermal dysplasia (HED). Am J Med Genet. 2001 Apr 22;100(2):164-8. Erratum in: Am J Med Genet 2001 Sep 1;102(4):394. (http://www.ncbi.nlm.nih.gov/pubmed/11298380?dopt=Abstract)
  • Fujimoto A, Kurban M, Nakamura M, Farooq M, Fujikawa H, Kibbi AG, Ito M, Dahdah M, Matta M, Diab H, Shimomura Y. GJB6, of which mutations underlie Clouston syndrome, is a potential direct target gene of p63. J Dermatol Sci. 2013 Feb;69(2):159-66. doi: 10.1016/j.jdermsci.2012.11.005. Epub 2012 Nov 16. (http://www.ncbi.nlm.nih.gov/pubmed/23219093?dopt=Abstract)
  • Gene Review: Hidrotic Ectodermal Dysplasia 2 (http://www.ncbi.nlm.nih.gov/books/NBK1200/)
  • Kibar Z, Der Kaloustian VM, Brais B, Hani V, Fraser FC, Rouleau GA. The gene responsible for Clouston hidrotic ectodermal dysplasia maps to the pericentromeric region of chromosome 13q. Hum Mol Genet. 1996 Apr;5(4):543-7. (http://www.ncbi.nlm.nih.gov/pubmed/8845850?dopt=Abstract)
  • Kibar Z, Dubé MP, Powell J, McCuaïg C, Hayflick SJ, Zonana J, Hovnanian A, Radhakrishna U, Antonarakis SE, Benohanian A, Sheeran AD, Stephan ML, Gosselin R, Kelsell DP, Christianson AL, Fraser FC, Der Kaloustian VM, Rouleau GA. Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping. Eur J Hum Genet. 2000 May;8(5):372-80. (http://www.ncbi.nlm.nih.gov/pubmed/10854098?dopt=Abstract)
  • Lamartine J, Munhoz Essenfelder G, Kibar Z, Lanneluc I, Callouet E, Laoudj D, Lemaître G, Hand C, Hayflick SJ, Zonana J, Antonarakis S, Radhakrishna U, Kelsell DP, Christianson AL, Pitaval A, Der Kaloustian V, Fraser C, Blanchet-Bardon C, Rouleau GA, Waksman G. Mutations in GJB6 cause hidrotic ectodermal dysplasia. Nat Genet. 2000 Oct;26(2):142-4. (http://www.ncbi.nlm.nih.gov/pubmed/11017065?dopt=Abstract)
  • Smith FJ, Morley SM, McLean WH. A novel connexin 30 mutation in Clouston syndrome. J Invest Dermatol. 2002 Mar;118(3):530-2. (http://www.ncbi.nlm.nih.gov/pubmed/11874494?dopt=Abstract)
  • Zhang XJ, Chen JJ, Yang S, Cui Y, Xiong XY, He PP, Dong PL, Xu SJ, Li YB, Zhou Q, Wang Y, Huang W. A mutation in the connexin 30 gene in Chinese Han patients with hidrotic ectodermal dysplasia. J Dermatol Sci. 2003 Jun;32(1):11-7. (http://www.ncbi.nlm.nih.gov/pubmed/12788524?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.

 
Reviewed: March 2014
Published: July 28, 2014