NORD gratefully acknowledges Gabriele Richard, MD, FACMG, Associate Scientific Director, GeneDx, Gaithersburg, Maryland, for assistance in the preparation of this report.
Progressive symmetric erythrokeratoderma (PSEK) is a rare genetic skin disorder characterized by well-demarcated plaques of reddened, dry, and thickened skin. These lesions are distributed symmetrically on the body and tend to slowly expand and progress over time. The severity and progression of the disorder can vary greatly from one person to another, even among members of the same family. PSEK is related and can be very similar in appearance to another rare disorder called erythrokeratodermia variabilis (EKV).
The symptoms of PSEK usually develop shortly after birth or during the first year of life. Infants develop reddened plaques of thickened, rough and scaly skin, especially on the face, buttocks, arms and legs. Over time, these lesions can cover large areas of the body. The distribution of these lesions is almost perfectly symmetrical, meaning the size, shape and location of the lesions are extremely similar on both sides of the body. These plaques are slowly progressive increasing in number and size throughout early childhood before either stabilizing or disappearing sometime later during life. Rarely, waxing and waning may occur. In some cases, the chest and abdomen may become involved. Abnormally thickened or calloused skin on the palms and soles (palmoplantar keratoderma) is not uncommon.
The exact cause of PSEK in the majority of affected individuals is not known. In one family described as having PSEK, researchers identified a mutation (genetic change) in the loricrin (LOR) gene. Other researchers maintained that these individuals may not have had PSEK, but rather a similar, yet different skin disorder caused by loricrin mutations called “Loricrin Keratoderma”.
In 2009, researchers identified two individuals who were given the clinical diagnosis of PSEK with a mutation in the connexin 30.3 gene (GJB4), which was also found in patients who clearly had erythrokeratodermia variabilis (EKV).
More research is necessary to identify and confirm the specific genetic mutation(s) that cause PSEK and to determine the exact underlying mechanisms involved in the development of the disorder.
PSEK is caused by a genetic mutation in an as of yet unidentified gene(s), which may occur at random (i.e., spontaneous new mutation) or be inherited as an autosomal dominant trait.
Genetic diseases are determined by specific genes associated with a particular trait. The genes are located on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from an affected parent to the offspring is 50 percent for each pregnancy regardless of the gender of the resulting child. To discuss the potential causes of PSEK, the risk of having children with this disorder and the possibility of genetic testing, genetic counseling may be of benefit for affected individuals and their families.
PSEK affects males and females in equal numbers. The prevalence of the disorder in the general population is unknown. The disorder was first described by Darier in 1911. Fewer than 100 cases have been described in the medical literature.
A diagnosis of PSEK is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and specialized tests including surgical removal and microscopic evaluation (biopsy) of affected tissue.
The treatment of PSEK is directed toward the specific symptoms that are apparent in each individual such as reducing the thickening and cracking of the skin. Affected individuals may also benefit from treatment with skin softening ointments (emollients) such as petroleum jelly. Some individuals with PSEK may also be treated with keratolytics. Keratolytics are drugs that cause the hardened outer layer of skin to come off (slough). Salicyclic acid is an example of a keratolytic agent that has been used to treat individuals with PSEK. Other keratolytics include lotions that contain alpha-hydroxy acids, propylene glycol, lactic acid or urea. Some individuals with severe PSEK may respond to therapy with retinoids. Retinoids are synthetic versions of vitamin A that are used to treat many different skin conditions, but may have serious side effects or adverse reactions.
Other treatment is symptomatic and supportive.
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James WD, Berger TG, Elston DM. Eds. Andrew’s Diseases of the Skin: Clinical Dermatology. 10th ed. Saunders. 2005:56.
Richard G. Progressive Symmetric Erythrokeratodermia/Erythrokeratodermia with Ataxia. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:111-112.
Singh S, Sharma S, Agarwal S, Nangia A, Chander R, Varghese B. Neutral lipid storage disease with unusual presentation: report of three cases. Pediatr Dermatol. 2012 May-Jun;29(3):341-4.
Van Steensel MA, Oranje AP, van der Schroeff JG, Wagner A, van Geel M. The missense mutation G12D in connexin30.3 can cause both erythrokeratodermia variabilis of Mendes da Costa and progressive symmetric erythrokeratodermia of Gottron. Am J Med Genet A. 2009;149A:657-661.
Cui Y, Yang S, Gao M, et al. Identification of a novel locus for progressive symmetric erythrokeratodermia to a 19.02-cM interval at 21q11.2-21q21.2. J Invest Dermatol. 2006;126:2136-2139.
Chu DH, Arroyo MP. Progressive and symmetric erythrokeratoderma. Dermatol J Online. 2003;9:21.
Ishida-Yamamoto A, McGrath J.A, Lam H, et al. The molecular pathology of progressive symmetric erythrokeratoderma: a frameshift mutation in the loricrin gene and perturbations in the cornified cell envelope. Am J Hum Genet. 1997;61:581-589.
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:133200; Last Update:09/11/2008. Available at: http://omim.org/entry/133200 Accessed:March 13, 2013.
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