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The prevalence of PPKP1 has been estimated at 1.17/100,000 in Croatia and 3.3/100,000 in Slovenia. PPKP1 has been reported in over 400 patients worldwide to date.

Typical clinical characteristics are multiple hyperkeratotic papules and central indentations that are irregularly distributed on the palms and soles. The lesions usually start to develop in early adolescence but can also present earlier or later in life. Sometimes additional confluent thickening of the soles can be observed. Depending on the clinical presentation, PPKP1 can be associated with pain at pressure points, especially on the soles. The lesions may coalesce over pressure points. There can be considerable variation between affected family members.

Mutations in the AAGAB gene (15q22.33-q23) have been identified as one of the causes of PPKP1. This gene encodes for the alpha and gamma-adaptin-binding protein p34 which is involved in the clathrin-mediated pathway and when disrupted causes an increase in the half-life of several receptor tyrosine kinases in basal keratinocytes, leading to hyperproliferation and hyperkeratosis. COL14A1 (8q24.12) is another gene that has been suggested to be implicated in the pathogenesis of PPKP1, but this association needs further confirmation, as it has only been reported once in a few cases from the same Chinese family.

Mutational analysis of the AAGAB gene and the COL14A1 gene confirms the clinical diagnosis. Although not specific for PPKP1, histological examination of papules reveals hypergranulosis and hyperkeratosis with a well-defined central epidermal depression.

Differential diagnosis includes verrucae vulgaris and any other form of palmoplantar keratoderma, primarily the focal types, such as porokeratosis punctata palmaris et plantaris (PPKP2) and focal acral hyperkeratosis (or PPKP3 without elastoidosis).

PPKP1 is inherited in an autosomal-dominant manner. Genetic counseling is possible.

Mechanical removal of the hyperkeratosis is the most effective symptomatic treatment. Keratolytic creams can support the treatment. In some patients with a severe phenotype, oral retinoids have been shown to reduce symptoms.

Although the clinical appearance of lesions can worsen over time, the general prognosis is good. Depending on the clinical severity and pain sensitivity of patients, quality of life can be affected.