Which are the causes of Palmoplantar Keratoderma?

Palmoplantar keratoderma (PPK) is a group of rare genetic disorders characterized by thickening of the skin on the palms of the hands and soles of the feet. This condition can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner, depending on the specific genetic mutation involved.

1. Genetic Mutations: The primary cause of PPK is genetic mutations that affect the proteins responsible for maintaining the normal structure and function of the skin. These mutations can lead to abnormal keratinization, resulting in the thickening of the skin on the palms and soles.

2. Autosomal Dominant PPK: In autosomal dominant PPK, a single copy of the mutated gene from one parent is sufficient to cause the condition. Several genes have been associated with this form of PPK, including KRT1, KRT9, and AAGAB. Mutations in these genes disrupt the normal keratinization process, leading to the development of thickened skin.

3. Autosomal Recessive PPK: Autosomal recessive PPK requires both copies of the gene to be mutated, one from each parent, for the condition to manifest. Mutations in genes such as TGM5, AQP5, and CSTA have been linked to autosomal recessive PPK. These mutations impair the skin's ability to retain moisture and regulate cell turnover, resulting in the characteristic thickening of the palms and soles.

4. X-Linked PPK: X-linked PPK is caused by mutations in the gene called GJB2, which is located on the X chromosome. This form of PPK predominantly affects males, as they have only one X chromosome. The GJB2 gene provides instructions for producing a protein called connexin 26, which is involved in the formation of gap junctions between cells. Mutations in this gene disrupt the normal functioning of connexin 26, leading to the development of PPK.

5. Other Factors: While genetic mutations are the primary cause of PPK, certain environmental factors and medical conditions can exacerbate the symptoms. Excessive friction, pressure, or trauma to the palms and soles can worsen the thickening of the skin. Additionally, certain systemic diseases, such as psoriasis, hypothyroidism, and malnutrition, can contribute to the development or progression of PPK.

It is important to note that PPK is a rare condition, and its specific causes may vary depending on the individual. Genetic testing and consultation with a dermatologist or genetic specialist are crucial for accurate diagnosis and appropriate management of PPK.