Keratosis palmoplantaris transgrediens et progrediens with mutations in slurp1 Q82.8; OMIM 248300

Autosomal recessive, inflammatory, palmoplantar keratosis with transition to the dorsum of the hands and feet.

Island of Mljet, Dalmatia, Anatolia; the frequency is estimated at 1:100,000 in the general population.

Among other things, autosomal recessive mutations of the SLURP1 gene (MDM gene), which is mapped on chromosome 8q, were described. The SLURP-1 gene encodes the SLURP1 protein (secreted mammalian Ly-6/uPAR-related protein 1). This protein can be addressed as an epidermal neuromodulator, which is important for epidermal homeostasis and inhibition of TNF-alpha release from macrophages, leading to hyperproliferation and inflammatory skin changes. It is also believed to have antitumoral activities.

A diffuse palmoplantacreratosis can be detected shortly after birth (3-10 months), transgenic pachydermia usually occurs before the age of 3 years.

Pronounced hyperkeratoses on planar erythema. Spread of hyperkeratoses during life to dorsum of hands, knuckles, forearms, dorsum of feet and lower legs (transgrediens). In addition, brachyphalangia, hyperhidrosis, pseudoainhum syndrome, and perioral erythema may be prominent. Nail involvement such as subungual keratoses or koilonychia is common. Diffuse hyperhidrosis leads to unpleasant body odor in affected individuals.

Occasionally, the occurrence of squamous cell carcinoma and melanoma has been reported in connection with the underlying disease.

This PKK variant was first described in persons from the Adriatic island of Meleda (Mljet), hence the name.

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