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Palmoplantar keratoderma with deafness

Reviewed November 2012

What is palmoplantar keratoderma with deafness?

Palmoplantar keratoderma with deafness is a disorder characterized by skin abnormalities and hearing loss. Affected individuals develop unusually thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma) beginning in childhood. Hearing loss ranges from mild to profound. It begins in early childhood and gets worse over time. Affected individuals have particular trouble hearing high-pitched sounds.

The signs and symptoms of this disorder may vary even within the same family, with some individuals developing only skin abnormalities and others developing only hearing loss.

How common is palmoplantar keratoderma with deafness?

Palmoplantar keratoderma with deafness is a rare disorder; its prevalence is unknown. At least 10 affected families have been identified.

What genes are related to palmoplantar keratoderma with deafness?

Palmoplantar keratoderma with deafness can be caused by mutations in the GJB2 or MT-TS1 genes.

The GJB2 gene provides instructions for making a protein called gap junction beta 2, more commonly known as connexin 26. Connexin 26 is a member of the connexin protein family. Connexin proteins form channels called gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. Gap junctions made with connexin 26 transport potassium ions and certain small molecules.

Connexin 26 is found in cells throughout the body, including the inner ear and the skin. In the inner ear, channels made from connexin 26 are found in a snail-shaped structure called the cochlea. These channels may help to maintain the proper level of potassium ions required for the conversion of sound waves to electrical nerve impulses. This conversion is essential for normal hearing. In addition, connexin 26 may be involved in the maturation of certain cells in the cochlea. Connexin 26 also plays a role in the growth, maturation, and stability of the outermost layer of skin (the epidermis).

The GJB2 gene mutations that cause palmoplantar keratoderma with deafness change single protein building blocks (amino acids) in connexin 26. The altered protein probably disrupts the function of normal connexin 26 in cells, and may interfere with the function of other connexin proteins. This disruption could affect skin growth and also impair hearing by disturbing the conversion of sound waves to nerve impulses.

Palmoplantar keratoderma with deafness can also be caused by a mutation in the MT-TS1 gene. This gene provides instructions for making a particular type of RNA, a molecule that is a chemical cousin of DNA. This type of RNA, called transfer RNA (tRNA), helps assemble amino acids into full-length, functioning proteins. The MT-TS1 gene provides instructions for a specific form of tRNA that is designated as tRNASer(UCN). This molecule attaches to a particular amino acid, serine (Ser), and inserts it into the appropriate locations in many different proteins.

The tRNASer(UCN) molecule is present only in cellular structures called mitochondria. These structures convert energy from food into a form that cells can use. Through a process called oxidative phosphorylation, mitochondria use oxygen, simple sugars, and fatty acids to create adenosine triphosphate (ATP), the cell's main energy source. The tRNASer(UCN) molecule is involved in the assembly of proteins that carry out oxidative phosphorylation.

The MT-TS1 gene mutation that causes palmoplantar keratoderma with deafness leads to reduced levels of tRNASer(UCN) to assemble proteins within mitochondria. Reduced production of proteins needed for oxidative phosphorylation may impair the ability of mitochondria to make ATP. Researchers have not determined why the effects of the mutation are limited to cells in the inner ear and the skin in this condition.

Related Gene(s)

Changes in these genes are associated with palmoplantar keratoderma with deafness.

  • GJB2
  • MT-TS1

How do people inherit palmoplantar keratoderma with deafness?

Palmoplantar keratoderma with deafness can have different inheritance patterns. When this disorder is caused by GJB2 gene mutations, it 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.

When palmoplantar keratoderma with deafness is caused by mutations in the MT-TS1 gene, it is inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mitochondrial DNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, only females pass mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children.

Where can I find information about diagnosis or management of palmoplantar keratoderma with deafness?

These resources address the diagnosis or management of palmoplantar keratoderma with deafness and may include treatment providers.

  • Foundation for Ichthyosis and Related Skin Types: Palmoplantar Keratodermas (http://www.firstskinfoundation.org/content.cfm/Ichthyosis/Palmoplantar-Keratodermas-PPK-Fact-Sheet/page_id/903)
  • Genetic Testing Registry: Keratoderma palmoplantar deafness (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1835672)

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

You may find the following resources about palmoplantar keratoderma with deafness 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 palmoplantar keratoderma with deafness?

  • palmoplantar hyperkeratosis-deafness syndrome
  • palmoplantar hyperkeratosis-hearing loss syndrome
  • palmoplantar keratoderma-deafness syndrome
  • palmoplantar keratoderma-hearing loss syndrome
  • PPK-deafness syndrome
  • PPK with deafness

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 palmoplantar keratoderma with deafness?

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

What glossary definitions help with understanding palmoplantar keratoderma with deafness?

acids ; adenosine triphosphate ; amino acid ; ATP ; autosomal ; autosomal dominant ; cell ; cochlea ; connexin ; DNA ; egg ; embryo ; epidermis ; fatty acids ; gap junctions ; gene ; inheritance ; ions ; keratoderma ; maternal ; maternal inheritance ; mitochondria ; molecule ; mutation ; oxidative phosphorylation ; oxygen ; palmoplantar keratoderma ; pattern of inheritance ; phosphorylation ; potassium ; prevalence ; protein ; RNA ; ser ; serine ; sperm ; syndrome ; transfer RNA ; tRNA

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

References

  • Birkenhäger R, Lüblinghoff N, Prera E, Schild C, Aschendorff A, Arndt S. Autosomal dominant prelingual hearing loss with palmoplantar keratoderma syndrome: Variability in clinical expression from mutations of R75W and R75Q in the GJB2 gene. Am J Med Genet A. 2010 Jul;152A(7):1798-802. doi: 10.1002/ajmg.a.33464. (http://www.ncbi.nlm.nih.gov/pubmed/20583176?dopt=Abstract)
  • Caria H, Matos T, Oliveira-Soares R, Santos AR, Galhardo I, Soares-Almeida L, Dias O, Andrea M, Correia C, Fialho G. A7445G mtDNA mutation present in a Portuguese family exhibiting hereditary deafness and palmoplantar keratoderma. J Eur Acad Dermatol Venereol. 2005 Jul;19(4):455-8. (http://www.ncbi.nlm.nih.gov/pubmed/15987292?dopt=Abstract)
  • de Zwart-Storm EA, Hamm H, Stoevesandt J, Steijlen PM, Martin PE, van Geel M, van Steensel MA. A novel missense mutation in GJB2 disturbs gap junction protein transport and causes focal palmoplantar keratoderma with deafness. J Med Genet. 2008 Mar;45(3):161-6. Epub 2007 Nov 9. (http://www.ncbi.nlm.nih.gov/pubmed/17993581?dopt=Abstract)
  • de Zwart-Storm EA, van Geel M, van Neer PA, Steijlen PM, Martin PE, van Steensel MA. A novel missense mutation in the second extracellular domain of GJB2, p.Ser183Phe, causes a syndrome of focal palmoplantar keratoderma with deafness. Am J Pathol. 2008 Oct;173(4):1113-9. doi: 10.2353/ajpath.2008.080049. Epub 2008 Sep 11. (http://www.ncbi.nlm.nih.gov/pubmed/18787097?dopt=Abstract)
  • Feldmann D, Denoyelle F, Blons H, Lyonnet S, Loundon N, Rouillon I, Hadj-Rabia S, Petit C, Couderc R, Garabédian EN, Marlin S. The GJB2 mutation R75Q can cause nonsyndromic hearing loss DFNA3 or hereditary palmoplantar keratoderma with deafness. Am J Med Genet A. 2005 Aug 30;137(2):225-7. (http://www.ncbi.nlm.nih.gov/pubmed/16059934?dopt=Abstract)
  • Iossa S, Chinetti V, Auletta G, Laria C, De Luca M, Rienzo M, Giannini P, Delfino M, Ciccodicola A, Marciano E, Franzé A. New evidence for the correlation of the p.G130V mutation in the GJB2 gene and syndromic hearing loss with palmoplantar keratoderma. Am J Med Genet A. 2009 Feb 15;149A(4):685-8. doi: 10.1002/ajmg.a.32462. (http://www.ncbi.nlm.nih.gov/pubmed/18688874?dopt=Abstract)
  • Lee JR, White TW. Connexin-26 mutations in deafness and skin disease. Expert Rev Mol Med. 2009 Nov 19;11:e35. doi: 10.1017/S1462399409001276. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19939300?dopt=Abstract)
  • Lee JY, In SI, Kim HJ, Jeong SY, Choung YH, Kim YC. Hereditary palmoplantar keratoderma and deafness resulting from genetic mutation of Connexin 26. J Korean Med Sci. 2010 Oct;25(10):1539-42. doi: 10.3346/jkms.2010.25.10.1539. Epub 2010 Sep 17. (http://www.ncbi.nlm.nih.gov/pubmed/20890442?dopt=Abstract)
  • Maász A, Komlósi K, Hadzsiev K, Szabó Z, Willems PJ, Gerlinger I, Kosztolányi G, Méhes K, Melegh B. Phenotypic variants of the deafness-associated mitochondrial DNA A7445G mutation. Curr Med Chem. 2008;15(13):1257-62. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18537605?dopt=Abstract)
  • Xu J, Nicholson BJ. The role of connexins in ear and skin physiology - functional insights from disease-associated mutations. Biochim Biophys Acta. 2013 Jan;1828(1):167-78. doi: 10.1016/j.bbamem.2012.06.024. Epub 2012 Jul 13. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22796187?dopt=Abstract)
  • Yuan Y, Huang D, Yu F, Zhu X, Kang D, Yuan H, Han D, Dai P. A de novo GJB2 (connexin 26) mutation, R75W, in a Chinese pedigree with hearing loss and palmoplantar keratoderma. Am J Med Genet A. 2009 Feb 15;149A(4):689-92. doi: 10.1002/ajmg.a.32461. (http://www.ncbi.nlm.nih.gov/pubmed/18924167?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: November 2012
Published: July 7, 2014