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

Reviewed December 2015

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.

Almost everyone with pachyonychia congenita has hypertrophic nail dystrophy, which causes the fingernails and toenails to become thick 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; 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 voice box (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 several genes, including KRT6A, KRT6B, KRT6C, KRT16, and KRT17, can cause pachyonychia congenita. All of 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, KRT6C gene mutations cause PC-K6c, KRT16 gene mutations cause PC-K16, and KRT17 gene mutations cause PC-K17.

Mutations in keratin genes alter the structure of keratin proteins, which prevents these proteins 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
  • KRT6C

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 a new (de novo) mutation in the gene that occurs during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases 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 4 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3714949)
  • 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 (https://www.nlm.nih.gov/medlineplus/ency/article/003247.htm)
  • MedlinePlus Encyclopedia: Natal Teeth (https://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 and 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 (https://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding pachyonychia congenita?

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

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References

  • Eliason MJ, Leachman SA, Feng BJ, Schwartz ME, Hansen CD. A review of the clinical phenotype of 254 patients with genetically confirmed pachyonychia congenita. J Am Acad Dermatol. 2012 Oct;67(4):680-6. doi: 10.1016/j.jaad.2011.12.009. Epub 2012 Jan 20. (http://www.ncbi.nlm.nih.gov/pubmed/22264670?dopt=Abstract)
  • Gene Review: Pachyonychia Congenita (http://www.ncbi.nlm.nih.gov/books/NBK1280)
  • 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)
  • O'Toole EA, Kaspar RL, Sprecher E, Schwartz ME, Rittié L. Pachyonychia congenita cornered: report on the 11th Annual International Pachyonychia Congenita Consortium Meeting. Br J Dermatol. 2014 Nov;171(5):974-7. doi: 10.1111/bjd.13341. Epub 2014 Oct 15. (http://www.ncbi.nlm.nih.gov/pubmed/25124823?dopt=Abstract)
  • Shah S, Boen M, Kenner-Bell B, Schwartz M, Rademaker A, Paller AS. Pachyonychia congenita in pediatric patients: natural history, features, and impact. JAMA Dermatol. 2014 Feb;150(2):146-53. doi: 10.1001/jamadermatol.2013.6448. (http://www.ncbi.nlm.nih.gov/pubmed/24132595?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)
  • Wilson NJ, O'Toole EA, Milstone LM, Hansen CD, Shepherd AA, Al-Asadi E, Schwartz ME, McLean WH, Sprecher E, Smith FJ. The molecular genetic analysis of the expanding pachyonychia congenita case collection. Br J Dermatol. 2014 Aug;171(2):343-55. doi: 10.1111/bjd.12958. Epub 2014 Aug 6. (http://www.ncbi.nlm.nih.gov/pubmed/24611874?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: December 2015
Published: February 8, 2016