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Genetics Home Reference: your guide to understanding genetic conditions
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Pachyonychia congenita

Reviewed August 2012

What is pachyonychia congenita?

Pachyonychia congenita is a condition that primarily affects the nails and skin. The signs and symptoms of this condition usually become apparent within the first few months of life, although a rare form of the condition known as pachyonychia congenita tarda appears in adolescence or early adulthood.

Almost everyone with pachyonychia congenita has hypertrophic nail dystrophy, which causes the fingernails and toenails to become thickened and abnormally shaped. Many affected children also develop very painful blisters and calluses on the soles of the feet and, less commonly, on the palms of the hands. This condition is known as palmoplantar keratoderma. Severe blisters and calluses on the feet can make it painful or impossible to walk.

Pachyonychia congenita can have several additional features, which vary among affected individuals. These features include thick, white patches on the tongue and inside of the cheeks (oral leukokeratosis); bumps called follicular keratoses that develop around hair follicles on the elbows, knees, and waistline; cysts in the armpits, groin, back, or scalp; brittle, coarse hair; and excessive sweating on the palms and soles (palmoplantar hyperhidrosis). Some affected individuals also develop widespread cysts called steatocystomas, which are filled with an oily substance called sebum that normally lubricates the skin and hair. Some babies with pachyonychia congenita have prenatal or natal teeth, which are teeth that are present at birth or in early infancy. Rarely, pachyonychia congenita can affect the voicebox (larynx), potentially leading to hoarseness or breathing problems.

Researchers used to split pachyonychia congenita into two types, PC-1 and PC-2, based on the genetic cause and pattern of signs and symptoms. However, as more affected individuals were identified, it became clear that the features of the two types overlapped considerably. Now researchers prefer to describe pachyonychia congenita based on the gene that is altered.

How common is pachyonychia congenita?

Although the prevalence of pachyonychia congenita is unknown, it appears to be rare. There are probably several thousand people worldwide with this disorder.

What genes are related to pachyonychia congenita?

Mutations in the KRT6A, KRT6B, KRT16, and KRT17 genes can cause pachyonychia congenita. These genes provide instructions for making tough, fibrous proteins called keratins. These proteins form networks that provide strength and resilience to the tissues that make up the skin, hair, and nails.

When pachyonychia congenita is caused by mutations in the KRT6A gene, it is classified as PC-K6a. Similarly, KRT6B gene mutations cause PC-K6b, KRT16 gene mutations cause PC-K16, and KRT17 gene mutations cause PC-K17. In other cases, the cause of the condition is unknown. These cases are classified as PC-U.

Mutations in any of the keratin genes listed above alter the structure of a keratin protein, which prevents keratins from forming strong, stable networks within cells. Without this network, skin cells become fragile and are easily damaged, making the skin less resistant to friction and minor trauma. Even normal activities such as walking can cause skin cells to break down, resulting in the formation of severe, painful blisters and calluses. Defective keratins also disrupt the growth and function of cells in the hair follicles and nails, resulting in the other features of pachyonychia congenita.

Related Gene(s)

Changes in these genes are associated with pachyonychia congenita.

  • KRT16
  • KRT17
  • KRT6A
  • KRT6B

How do people inherit pachyonychia congenita?

Pachyonychia congenita is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about half of all cases, an affected person inherits the mutation from one affected parent. The other half of 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 pachyonychia congenita?

These resources address the diagnosis or management of pachyonychia congenita and may include treatment providers.

  • Gene Review: Pachyonychia Congenita (http://www.ncbi.nlm.nih.gov/books/NBK1280)
  • Genetic Testing Registry: Pachyonychia congenita, type 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1706595)
  • Genetic Testing Registry: Pachyonychia congenita syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265334)
  • Genetic Testing Registry: Pachyonychia congenita type 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1721007)
  • MedlinePlus Encyclopedia: Nail Abnormalities (http://www.nlm.nih.gov/medlineplus/ency/article/003247.htm)
  • MedlinePlus Encyclopedia: Natal Teeth (http://www.nlm.nih.gov/medlineplus/ency/article/003268.htm)

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

You may find the following resources about pachyonychia congenita 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 pachyonychia congenita?

  • congenital pachyonychia
  • Jackson-Lawler syndrome (PC-2)
  • Jadassohn-Lewandowski syndrome (PC-1)
  • pachyonychia congenita syndrome

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 pachyonychia congenita?

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

What glossary definitions help with understanding pachyonychia congenita?

autosomal ; autosomal dominant ; cell ; congenital ; cysts ; dysplasia ; gene ; groin ; hyperhidrosis ; hypertrophic ; keratin ; keratoderma ; leukokeratosis ; mutation ; pachyonychia ; palmoplantar keratoderma ; prenatal ; prevalence ; protein ; resilience ; syndrome ; trauma

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

References

  • Gene Review: Pachyonychia Congenita (http://www.ncbi.nlm.nih.gov/books/NBK1280)
  • Leachman SA, Kaspar RL, Fleckman P, Florell SR, Smith FJ, McLean WH, Lunny DP, Milstone LM, van Steensel MA, Munro CS, O'Toole EA, Celebi JT, Kansky A, Lane EB. Clinical and pathological features of pachyonychia congenita. J Investig Dermatol Symp Proc. 2005 Oct;10(1):3-17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16250204?dopt=Abstract)
  • Liao H, Sayers JM, Wilson NJ, Irvine AD, Mellerio JE, Baselga E, Bayliss SJ, Uliana V, Fimiani M, Lane EB, McLean WH, Leachman SA, Smith FJ. A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita. J Dermatol Sci. 2007 Dec;48(3):199-205. Epub 2007 Aug 24. (http://www.ncbi.nlm.nih.gov/pubmed/17719747?dopt=Abstract)
  • McLean WH, Hansen CD, Eliason MJ, Smith FJ. The phenotypic and molecular genetic features of pachyonychia congenita. J Invest Dermatol. 2011 May;131(5):1015-7. doi: 10.1038/jid.2011.59. Epub 2011 Mar 24. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21430705?dopt=Abstract)
  • McLean WH, Smith FJ, Cassidy AJ. Insights into genotype-phenotype correlation in pachyonychia congenita from the human intermediate filament mutation database. J Investig Dermatol Symp Proc. 2005 Oct;10(1):31-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16250207?dopt=Abstract)
  • Smith FJ, Liao H, Cassidy AJ, Stewart A, Hamill KJ, Wood P, Joval I, van Steensel MA, Björck E, Callif-Daley F, Pals G, Collins P, Leachman SA, Munro CS, McLean WH. The genetic basis of pachyonychia congenita. J Investig Dermatol Symp Proc. 2005 Oct;10(1):21-30. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16250206?dopt=Abstract)
  • Terrinoni A, Smith FJ, Didona B, Canzona F, Paradisi M, Huber M, Hohl D, David A, Verloes A, Leigh IM, Munro CS, Melino G, McLean WH. Novel and recurrent mutations in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia congenita. J Invest Dermatol. 2001 Dec;117(6):1391-6. (http://www.ncbi.nlm.nih.gov/pubmed/11886499?dopt=Abstract)
  • Wilson NJ, Leachman SA, Hansen CD, McMullan AC, Milstone LM, Schwartz ME, McLean WH, Hull PR, Smith FJ. A large mutational study in pachyonychia congenita. J Invest Dermatol. 2011 May;131(5):1018-24. doi: 10.1038/jid.2011.20. Epub 2011 Feb 17. (http://www.ncbi.nlm.nih.gov/pubmed/21326300?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: August 2012
Published: March 23, 2015