Plantar palmar keratoderma (PPK) is an umbrella term for a group of heterogeneous disorders, acquired or inherited, characterized by hyperkeratosis of the palmar and/or plantar surfaces. Point PPK (PPPK) has been shown to have an autosomal dominant genotype. It is associated with two loci on chromosomes 8q24.13-8q24.21 and 15q22-15q24. In type 1 PPPK, also known as Buschke-Fischer-Brauer disease, loss-of-function mutations in either wonder or the COL14A1 Genes have been associated with this disorder. Here we report the clinical and genetic features of the patient with findings most consistent with type 1 PPPK.
Plantar palmar keratoderma (PPK) is an umbrella term for a group of heterogeneous disorders, acquired or inherited, characterized by hyperkeratosis of the palmar and/or plantar surfaces. Three clinical patterns of PPK have been described: diffuse, focal (with widespread hyperkeratosis at points of friction), and dotted. . PPKs are usually distinguished on the basis of morphology and distribution of lesions, histopathological findings, method of genotype, and additional cutaneous and systemic manifestations.
Point PPK (PPPK) has been shown to have an autosomal dominant genotype. It is associated with two loci on chromosomes 8q24.13-8q24.21 and 15q22-15q24. . In type 1 PPPK, also known as Buschke-Fischer-Brauer disease, loss-of-function mutations in either wonder or the COL14A1 Genes have been associated with this disorder . Here we report the clinical and genetic features of the patient with findings most consistent with type 1 PPPK.
A 36-year-old female, with a history of asthma, environmental allergies, and gastroesophageal reflux disease (GERD), with a 14-year history of asymptomatic, persistent, progressively increasing skin lesions on the palms of the hands and feet. Asthma and environmental allergies are well controlled with fluticasone propionate-salmeterol 250-50 mcg/inhalation dose once daily and levocetirizine 5 mg as one tablet taken by mouth once daily. GERD is controlled through dietary and lifestyle modifications. Her parents are not related. Her paternal grandfather, father, and three brothers all had similar lesions 1). Examination of the skin revealed multiple perforated hyperkeratotic papules, 0.3 to 0.4 cm in size, on the lateral aspects of the fingers, palms, and feet (Figs). 2And 3). There were no similar lesions elsewhere in the body. Hair, nails and mucous membranes were normal. The patient reported using a pumice stone to mechanically remove papules on her palms and soles.
Gene sequence analysis and deletion and duplication testing for wonder Gene testing on the peripheral blood sample revealed an inconclusive heterozygous variant [c.370C>T (p.Arg124*)] in exon 4 of wonder gene. This variant includes a known single nucleotide polymorphism (SNP), rs200564757. This SNP has a minor allele frequency of T = 0.00002509 in the analysis of the Genome Assembly Database (gnomAD) (https://gnomad.broadinstitute.org/), which aggregates all populations. To date, exome analysis has reported this mutation in African, European and Asian ancestral backgrounds. No rare variants were found in COL14A1 gene. Based on the above clinical-pathological findings, type 1 palmoplantar keratoderma was diagnosed. A biopsy of the lesion was not performed. He reassured the patient and started taking 40% urea lotion.
Palmar plantar keratoses (PPKs) are a family of diseases characterized by hyperkeratosis of the palms and soles. PPKs can occur in families in different genotypes, including an autosomal recessive, autosomal dominant, mitochondrial, or possibly an X-linked recessive trait . The severity of the clinical picture between family and within family shows wide variation . PPKs are clinically classified into three major categories according to the area of the palms and soles affected: diffuse, focal, and dotted. [1-2]. The palm and sole are subject to a high level of physical stress in daily use. In mechanically irritated areas, such as these, confluent plaques may be found . PPKs show genetic heterogeneity and have been associated with genes coding for components of intermediate filaments, desmosome channels, and vacuolar junctions. .
the wonder The gene consists of 10 exons with a coding sequence of 945 nucleotides. wonder It is described everywhere by matrix analysis . wonder It is associated with autosomal dominant papulopapular keratosis medulloblastoma or keratoderma maculopapularis type 1A (PPKP1A). Jill et al  showed that mutations in wonder leads to reduced expression of AAGAB protein in the skin of those with PPKP1A, supporting a role for AAGAB wonder in the pathogenesis of PPKP1A. PPKP1A, also known as Buschke-Fischer-Brauer disease, is a rare subtype of palmoplantar keratosis [2-4]. It is characterized by hyperkeratotic papules irregularly distributed across both the palmar and plantar surfaces. The papules may coalesce into larger plaques or acquire a warty aspect in areas of greatest pressure or friction such as the soles. The typical feature is exacerbation of papules after exposure to water . Lesions usually begin to appear in late childhood to early adulthood, with an onset age reported from 12 to 33 years of age. . Male patients are more commonly affected . It is a rare condition, with an estimated prevalence of 1.17 per 100,000 people . To date, more than 50 mutations in wonder Gene coding for the alpha- and gamma-binding protein p34 has been described in the literature [3-5,8-10]. There is no correlation between genotype and phenotype . The severity of symptoms is related to aging and environmental factors. There have been reports of an association between PPKP and the development of malignancies, including kidney, lung, gastrointestinal tract, and skin . Treatment options for PPKP1A include moisturizing creams, keratolytics (salicylic acid, lactic acid, and urea), topical retinoids, calcipotriene, topical 5-fluorouracil, and oral retinoids, while surgical options include cryosurgery, mechanical debridement, and excision.
We have reported a patient with a heterozygous variant wonder The gene leading to epidermal apical keratoderma type 1A (PPKP1A). Her grandfather, her father, and her three siblings all had hyperkeratotic perforated papules on the palms and soles that appeared in adolescence and became more severe with age with her older relatives. Prior to her appointment with the dermatology department, the patient had her palmar and plantar lesions treated by mechanical debridement. The urea lotion (40%), which was prescribed during her appointment, was expected to help manage her symptoms. Our findings support evidence in the literature that there are autosomal dominant mutations in wonder leads to PPKP1A.