Pachyonychia congenita

Pachyonychia congenita is a condition that primarily affects the nails and skin. The signs and symptoms of this condition usually become apparent within the first few months of life, although a rare form of the condition known as pachyonychia congenita tarda appears in adolescence or early adulthood.

Almost everyone with pachyonychia congenita has hypertrophic nail dystrophy, which causes the fingernails and toenails to become thickened and abnormally shaped. Many affected children also develop very painful calluses and blisters on the soles of the feet and, less commonly, on the palms of the hands. This condition is known as palmoplantar keratoderma. The blistering is most severe in weight-bearing areas and in other areas that experience trauma or friction. Severe blistering and callusing on the feet can make it painful or impossible to walk.

Additional features of pachyonychia congenita include thick, white patches on the tongue and inside of the cheeks (oral leukokeratosis); bumps called follicular keratoses that develop around hair follicles on the elbows, knees, and waistline; cysts in the armpits, groin, back, or scalp; and excessive sweating on the palms and soles (palmoplantar hyperhidrosis). Rarely, the condition can affect the voicebox (larynx), potentially leading to hoarseness or breathing problems. These features vary among affected individuals.

Researchers have described two major forms of pachyonychia congenita, type 1 (PC-1) and type 2 (PC-2). The two types are distinguished by their genetic cause and by their signs and symptoms. Both types are associated with the features described above, but PC-2 has several additional features that are not typically seen in PC-1. For example, most people with PC-2 develop widespread cysts called steatocystomas during puberty. People with PC-2 are also more likely to have hair that is twisted or kinked, brittle, and coarse. Additionally, some babies with PC-2 have prenatal or natal teeth, which are teeth that are present at birth or in early infancy.

Although the prevalence of pachyonychia congenita is unknown, it appears to be extremely rare. There are probably several thousand people worldwide with this disorder.

Mutations in the KRT6A, KRT6B, KRT16, and KRT17 genes can cause pachyonychia congenita. These genes provide instructions for making proteins called keratins. Keratins are tough, fibrous proteins that provide strength and resiliency to the tissues that make up the skin, hair, and nails.

Mutations in the KRT6A or KRT16 gene result in PC-1, while mutations in KRT6B or KRT17 result in PC-2. Mutations in any of these genes alter the structure of a keratin protein, which prevents keratins from forming strong, stable networks within cells. Without this network, skin cells become fragile and are easily damaged, making the skin less resistant to friction and minor trauma. Defective keratins also disrupt the growth and function of cells in the hair follicles and nails, which leads to the other features of pachyonychia congenita.

Read more about the KRT6A, KRT6B, KRT16, and KRT17 genes.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

It is estimated that in half of all cases, an affected person inherits the mutation from one affected parent. The other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.