Peeling skin syndrome 2

Peeling skin syndrome 2 is a skin disorder characterized by painless peeling of the top layer of skin. In this form of peeling skin syndrome, the peeling is most apparent on the hands and feet. Occasionally, peeling also occurs on the arms and legs. The peeling usually starts soon after birth, although the condition can also begin in childhood or later in life. 

Skin peeling is made worse by exposure to heat, humidity and other forms of moisture, and friction. The underlying skin may be temporarily red and itchy, but it typically heals without scarring. Peeling skin syndrome 2 is not associated with any other health problems.

Peeling skin syndrome 2 is a rare condition, with a few dozen cases reported in the medical literature. However, because its signs and symptoms tend to be mild and similar to those of other skin disorders, the condition is likely underdiagnosed.

Peeling skin syndrome 2 is caused by variants (also called mutations) in the TGM5 gene. This gene provides instructions for making an enzyme called transglutaminase 5, which is part of the outer layer of skin (the epidermis). Transglutaminase 5 plays a critical role in the formation of a structure called the cornified cell envelope, which surrounds epidermal cells and helps the skin form a protective barrier between the body and its environment.

TGM5 gene variants reduce the activity of transglutaminase 5 or prevent cells from making any of this enzyme. A shortage of transglutaminase 5 weakens the cornified cell envelope, which allows the outermost cells of the epidermis to separate easily from the underlying skin and peel off. The peeling may be most noticeable on the hands and feet because those areas are more often exposed to moisture and friction.

Genetic Testing Information

• Genetic Testing Registry: Acral peeling skin syndrome

Genetic and Rare Diseases Information Center

• Acral peeling skin syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• PEELING SKIN SYNDROME 2; PSS2

Scientific Articles on PubMed

• PubMed

• Cassidy AJ, van Steensel MA, Steijlen PM, van Geel M, van der Velden J, Morley SM, Terrinoni A, Melino G, Candi E, McLean WH. A homozygous missense mutation in TGM5 abolishes epidermal transglutaminase 5 activity and causes acral peeling skin syndrome. Am J Hum Genet. 2005 Dec;77(6):909-17. doi: 10.1086/497707. Epub 2005 Oct 11. Citation on PubMed or Free article on PubMed Central
• Kiritsi D, Cosgarea I, Franzke CW, Schumann H, Oji V, Kohlhase J, Bruckner-Tuderman L, Has C. Acral peeling skin syndrome with TGM5 gene mutations may resemble epidermolysis bullosa simplex in young individuals. J Invest Dermatol. 2010 Jun;130(6):1741-6. doi: 10.1038/jid.2010.23. Epub 2010 Feb 18. No abstract available. Citation on PubMed
• Pavlovic S, Krunic AL, Bulj TK, Medenica MM, Fong K, Arita K, McGrath JA. Acral peeling skin syndrome: a clinically and genetically heterogeneous disorder. Pediatr Dermatol. 2012 May-Jun;29(3):258-63. doi: 10.1111/j.1525-1470.2011.01563.x. Epub 2011 Nov 8. Citation on PubMed
• Pigors M, Kiritsi D, Cobzaru C, Schwieger-Briel A, Suarez J, Faletra F, Aho H, Makela L, Kern JS, Bruckner-Tuderman L, Has C. TGM5 mutations impact epidermal differentiation in acral peeling skin syndrome. J Invest Dermatol. 2012 Oct;132(10):2422-2429. doi: 10.1038/jid.2012.166. Epub 2012 May 24. Citation on PubMed
• Szczecinska W, Nesteruk D, Wertheim-Tysarowska K, Greenblatt DT, Baty D, Browne F, Liu L, Ozoemena L, Terron-Kwiatkowski A, McGrath JA, Mellerio JE, Morton J, Wozniak K, Kowalewski C, Has C, Moss C. Under-recognition of acral peeling skin syndrome: 59 new cases with 15 novel mutations. Br J Dermatol. 2014 Nov;171(5):1206-10. doi: 10.1111/bjd.12964. Epub 2014 Oct 20. Citation on PubMed