Which are the causes of Mal de Meleda?

Mal de Meleda is a rare genetic disorder that affects the skin. It is characterized by thickening of the skin on the palms of the hands and soles of the feet, which gradually extends to other parts of the body. The exact cause of Mal de Meleda is not fully understood, but it is believed to be caused by mutations in the ARS (AP2S1) gene.

Genetic Mutations: Mal de Meleda is an autosomal recessive disorder, which means that both parents must carry a mutated copy of the ARS gene for their child to be affected. When both parents are carriers, there is a 25% chance with each pregnancy that the child will inherit two mutated copies of the gene and develop the condition. The ARS gene provides instructions for producing a protein that is involved in the transport of molecules within cells. Mutations in this gene disrupt the normal functioning of the protein, leading to the characteristic thickening of the skin.

Family History: Individuals with a family history of Mal de Meleda are at an increased risk of developing the condition. If one or both parents carry a mutated copy of the ARS gene, there is a possibility that their children may inherit the disorder. Genetic counseling can help assess the risk and provide guidance for families with a history of Mal de Meleda.

Environmental Factors: While genetic mutations play a significant role in the development of Mal de Meleda, certain environmental factors may also contribute to the severity and progression of the condition. Factors such as exposure to irritants, trauma to the skin, and infections can exacerbate the symptoms and lead to complications.

Other Contributing Factors: Some studies suggest that certain hormonal imbalances and immune system abnormalities may also influence the development of Mal de Meleda. However, further research is needed to fully understand the role of these factors in the disorder.

Conclusion: Mal de Meleda is a rare genetic disorder caused by mutations in the ARS gene. It is inherited in an autosomal recessive manner and can be passed down through generations. While the exact cause is not fully understood, genetic mutations and environmental factors are believed to contribute to the development and progression of the condition. Understanding the causes of Mal de Meleda is crucial for genetic counseling, early diagnosis, and potential future treatments.