Pachyonychia Congenita (pachyonychia congenital) - Genes KRT6A, KRT6B, KRT6C, KRT16 and KRT17            

Pachyonychia congenita is a disorder that primarily affects the nails and skin. Signs and symptoms of this disease are usually evident in the first months of life, although a rare form of the disease known as congenital pachyonychia manifests itself in late adolescence or early adulthood.

The manifestations of the disease include hypertrophic nail dystrophy, which causes the fingernails and feet are thicker and become abnormally; very painful blisters and calluses on the soles of the feet and, less often, on the palms of the hands, which is known as palmoplantar keratoderma; oral leukokeratosis; follicular keratosis that develops around the hair follicles on the elbows, knees and waist; cysts in the armpits, groin, back or scalp; brittle and coarse hair; and hyperhidrosis palmoplantar. Some affected individuals also develop steatocystomas. 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);   and the KRT16 (Keratin 16) and KRT17 (Keratin 17) gene, located on the long arm of chromosome 17 (17q21.2). These genes encode proteins keratins, forming networks that provide strength and elasticity to tissues that make up the skin, hair and nails. When pachyonychia congenita is caused by mutations in the gene KRT6A, it is classified as PC-K6a. Similarly, mutations of genes cause KRT6B PC-K6b, mutations of genes cause KRT6C PC-K6C, KRT16 mutations cause PC-K16 genes and gene mutations cause KRT17 PC-K17.

They have identified at least 40 mutations in the gene KRT6A, 4 mutations in the gene KRT6B, 4 mutations in the gene KRT6C, 19 mutations in the gene KRT16 and more than 20 mutations in the gene KRT17 in people with congenital pachyonychia. Mutations in either gene alter the structure of keratin protein, which prevents the formation of networks strong and stable within cells keratins. Without this network, 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 the skin cells degrade, which causes severe blistering and painful corns. Defective keratins also alter the growth and function of cells in hair follicles and nails, leading to the other features of the disease.  

Pachyonychia congenita is considered an autosomal dominant disease, which means that a copy of the altered gene in each cell is sufficient for the disease to be expressed. In about half of all cases, an affected person inherits the mutation from an affected parent. The other half of the new cases are due to 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 disease in your family.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with Pachyonychia Congenita, by complete PCR amplification of the exons of KRT6A, KRT6B, KRT6C, KRT16 and KRT17, respectively, genes and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).