Progressive Symmetric Erythrokeratodermia
NORD is very grateful to Gabriele Richard, MD, FACMG, Associate Scientific Director, GeneDx, Gaithersburg, Maryland, for assistance in the preparation of this report.
Synonyms of Progressive Symmetric Erythrokeratodermia
- Darier-Gottron syndrome
- progressive symmetric erythrokeratoderma
- progressive symmetric erythrokeratodermia of Gottron
- No subdivisions found.
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.
Symptoms of the following disorders can be similar to those of PSEK. Comparisons may be useful for a differential diagnosis.
Other forms of ichthyosis or disorders of cornification, such as Neutral lipid storage disease with ichthyosis, may present with reddened, thickened or scaly skin but usually involve the entire body, may have variable other hair, nail, eye, hearing and additional abnormalities, and are often inherited as autosomal recessive traits. Ichthyosis in general terms describes a group of generalized scaly skin disorders. (For more information on these disorders, choose "ichthyosis" as your search term in the Rare Disease Database.)
PSEK shares many overlapping features with erythrokeratodermia variabilis (EKV). In these disorders, a person develops red, rough thickened plaques of skin, especially on the arms and legs. In EKV, the lesions are extremely similar to the lesions found in PSEK and also appear during early infancy and often develop symmetrically. However, in EKV the plaques are less stable and may move to other areas of the body (migratory), while in PSEK they remain fixed. In addition, lesions are much less likely to develop on the face in individuals with EKV. The hallmark of EKV is the recurrent appearance of sharply outlined red spots (erythema), which only last for hours or days, often triggered by sudden temperature changes and other factors. Those fleeting erythema are not seen in PSEK. EKV is inherited as an autosomal dominant trait. Most cases of EKV are caused by mutation in the connexin 31 (GJB3) or connexin 30.3 (GJB4) genes. (For more information on this disorder, choose "erythrokeratoderma variabilis" as your search term in the Rare Disease Database.)
Psoriasis is a chronic, inflammatory skin disease characterized by dry, reddish (erythematous), thickened patches of skin that are covered with silvery-gray scales. These patches may be referred to as papules or plaques and most often affect the scalp, elbows, knees, hands, feet and/or lower back. The plaques may be intensely itchy (pruritis) or sore. In some cases, individuals with psoriasis may experience abnormalities affecting the fingernails, toenails, and the soft tissues inside the mouth. The severity of psoriasis varies from case to case. Psoriasis may be classified as mild, moderate or severe depending upon the amount of skin involved and the effect on an individual’s quality of life. In approximately one-third of cases a family history of psoriasis is present. (For more information on this disorder, choose "psoriasis" as your search term in the Rare Disease Database.)
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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Progressive Symmetric Erythrokeratodermia Resources
NORD Member Organizations:
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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.
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