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Punctate palmoplantar keratoderma type 1
Punctate palmoplantar keratoderma type I (PPKP1), also known as Buschke-Fischer-Brauer syndrome, is a very rare hereditary skin disease characterized by irregularly distributed epidermal hyperkeratosis of the palms and soles with wide variation among patients..
The prevalence of PPK1 has been estimated at 1.17/100,000 in Croatia and 3.3/100,000 in Slovenia. PPK1 has been reported 35 families 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 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.
Mutations in the AAGAB gene (15q22.33-q23) have recently 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. Mutations in the COL14A1 gene (8q23) have also been identified as causal in some cases in Asia that seem to have a similar phenotype.
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 vulgares and any other form of palmoplantar keratoderma (see this term).
PPKP1 is mostly inherited in an autosomal-dominant manner. Genetic counseling is possible.
Management and treatment
Mechanical removal of the hyperkeratosis is the most effective symptomatic treatment. Keratolytic creams can support the effect. In some patients with a severe phenotype, oral retinoids have been shown to reduce the symptoms.
Although the clinical appearance 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.