Which are the causes of Pachyonychia Congenita?

Pachyonychia Congenita (PC) is a rare genetic disorder that primarily affects the nails, skin, hair, and mucous membranes. It is caused by mutations in one of five genes: KRT6A, KRT6B, KRT6C, KRT16, or KRT17. These genes provide instructions for making proteins called keratins, which are essential for the structural integrity of the skin, hair, and nails.

1. KRT6A, KRT6B, and KRT6C Mutations: Mutations in the KRT6A, KRT6B, and KRT6C genes are associated with PC type 1 (PC-1). These genes produce keratin 6 proteins, which are primarily found in the nails, hair follicles, and sweat glands. The mutations disrupt the normal structure and function of these keratins, leading to the characteristic features of PC-1.

2. KRT16 and KRT17 Mutations: Mutations in the KRT16 and KRT17 genes are associated with PC type 2 (PC-2). These genes produce keratin 16 and keratin 17 proteins, which are found in the skin, nails, and other epithelial tissues. The mutations in these genes also result in abnormal keratin production, leading to the symptoms of PC-2.

3. Inheritance: Pachyonychia Congenita is inherited in an autosomal dominant manner, which means that a person only needs to inherit one copy of the mutated gene from either parent to develop the disorder. However, in some cases, PC can also occur due to spontaneous mutations that are not inherited.

4. Clinical Features: The most prominent clinical features of PC include thickened nails (pachyonychia), painful calluses on the soles of the feet (plantar keratoderma), blistering and redness of the palms and soles (palmoplantar keratoderma), cysts in the sweat glands (steatocystoma), and oral leukokeratosis (white patches in the mouth). These symptoms can vary in severity and may appear at birth or develop later in childhood.

5. Treatment: Currently, there is no cure for Pachyonychia Congenita, and treatment mainly focuses on managing the symptoms. This may involve regular trimming and filing of the nails, using keratolytic agents to reduce calluses, and applying moisturizers to alleviate dry skin. Pain management strategies, such as the use of analgesics or local anesthetics, may be employed to relieve discomfort caused by the condition.

In conclusion, Pachyonychia Congenita is a rare genetic disorder caused by mutations in specific keratin genes. These mutations disrupt the normal structure and function of keratins, leading to the characteristic symptoms of PC. While there is no cure, various treatment options are available to manage the symptoms and improve the quality of life for individuals with this condition.