Pachyonychia congenital - KRT6A, KRT6B, KRT6C, KRT16 and KRT17 genes           

Congenital pachyonychia is an alteration that mainly affects the nails and skin. The signs and symptoms of this disease usually become evident in the first months of life, despite the fact that a rare form of the disease, known as late congenital pachionychia, manifests itself in adolescence or early adulthood.

The manifestations of the disease include hypertrophic nail dystrophy, which causes the nails of the hands and feet to become thicker and abnormally shaped; very painful blisters and calluses on the soles of the feet, and less frequently on the palms of what is known as palmoplantar keratoderma. Other clinical signs include: oral leukokeratosis; follicular keratosis around the hair follicles on the elbows, knees and waist; cysts in the armpits, groin, back or scalp; brittle and rough hair; and palmoplantar hyperhidrosis. Some affected individuals also develop steatocistomas. Some newborns have prenatal or natal teeth. Rarely, the disease affects the larynx, which can lead to hoarseness or difficulty breathing.

This process is due to mutations in the KRT6A (keratin 6A), KRT6B (keratin 6B) and KRT6C (keratin 6C) genes, located on the long arm of chromosome 12 (12q13.13), as well as the KRT16 (keratin 16) and KRT17 (keratin 17) genes, located on the long arm of chromosome 17 (17q21.2). These genes encode keratin proteins, which form networks that provide resistance and elasticity to the tissues that make up the skin, hair and nails. When congenital pachyonychia is due to mutations in the KRT6A gene, it is classified as PC-K6a. Similarly, KRT6B gene mutations cause PC-K6b, KRT6C gene mutations cause PC-K6c, KRT16 gene mutations cause PC-K16, and KRT17 gene mutations cause PC-K17.

At least 40 mutations in the KRT6A gene, 4 mutations in KRT6B, 4 mutations in KRT6C, 19 mutations in KRT16 and more than 20 mutations in KRT17 have been identified in people with congenital pachyonychia. Mutations in any of the genes alter the structure of a keratin protein, which prevents the formation of strong and stable keratin networks inside cells. Without this network the skin cells become fragile and easily damaged, making the skin less resistant to friction and minor trauma. Even normal activities such as walking can cause skin cells to degrade, which causes severe painful blisters and calluses. Defective keratins also alter the growth and function of cells in hair follicles and nails, leading to the other described characteristics of the disease. .

Congenital pachyonychia is considered an autosomal dominant disease, which means that one copy of the altered gene in each cell is sufficient for the disease to express itself. In about half of all cases, an affected person inherits the mutation of an affected parent. The other half of the cases are due to new mutations in the gene that occur during the formation of reproductive cells or early embryonic development. These cases occur in people with no history of the disease in their family.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with pachyonychia congenital, by means of the complete PCR amplification of the exons of the KRT6A, KRT6B, KRT6C, KRT16 and KRT17 genes, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leukocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).