Which are the causes of Peutz-Jeghers syndrome?

Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of polyps in the gastrointestinal tract and the presence of distinctive pigmented spots on the lips, oral mucosa, and other parts of the body. This autosomal dominant condition is caused by mutations in the STK11 gene, also known as LKB1, which plays a crucial role in regulating cell growth and division.

Genetic Mutations:

The primary cause of Peutz-Jeghers syndrome is the presence of germline mutations in the STK11 gene. These mutations are inherited from one affected parent and can be passed on to future generations. The STK11 gene provides instructions for making a protein that acts as a tumor suppressor, helping to prevent the uncontrolled growth of cells. However, mutations in this gene disrupt its normal function, leading to the development of polyps and other characteristic features of PJS.

Polyp Formation:

Polyps are abnormal tissue growths that can occur in various parts of the body, including the gastrointestinal tract. In Peutz-Jeghers syndrome, polyps primarily develop in the stomach, small intestine, and colon. The STK11 gene mutations disrupt the regulation of cell growth and division, leading to the formation of these polyps. The polyps in PJS are typically hamartomatous, which means they contain a mixture of different cell types and are not cancerous. However, if left untreated, these polyps can increase the risk of developing cancerous tumors.

Role of LKB1 Protein:

The LKB1 protein, encoded by the STK11 gene, is involved in several cellular processes that help maintain normal tissue function. It acts as a kinase, which means it adds phosphate groups to other proteins, thereby regulating their activity. LKB1 plays a crucial role in controlling cell growth, cell division, and cell movement. It also helps to maintain the balance between cell proliferation and cell death. Mutations in the STK11 gene disrupt the normal function of the LKB1 protein, leading to abnormal cell growth and the formation of polyps.

Inheritance Pattern:

Peutz-Jeghers syndrome follows an autosomal dominant inheritance pattern. This means that an individual with PJS has a 50% chance of passing the mutated gene to each of their children. Both males and females can inherit and transmit the condition. In some cases, PJS may occur due to a new mutation in the STK11 gene, without being inherited from a parent.

Other Factors:

While the primary cause of Peutz-Jeghers syndrome is the presence of STK11 gene mutations, other factors may influence the severity and specific features of the condition. Genetic modifiers, which are variations in other genes, can affect the expression of PJS and contribute to the variability in symptoms observed among affected individuals. Environmental factors and lifestyle choices, such as diet and exposure to certain toxins, may also influence the development and progression of polyps in individuals with PJS.

Conclusion:

Peutz-Jeghers syndrome is primarily caused by germline mutations in the STK11 gene, which disrupt the normal function of the LKB1 protein. This leads to the development of polyps in the gastrointestinal tract and the characteristic pigmented spots seen in PJS. The autosomal dominant inheritance pattern of the condition means that affected individuals have a 50% chance of passing on the mutated gene to their children. While genetic factors play a significant role, other genetic modifiers, environmental factors, and lifestyle choices may also contribute to the variability in symptoms and disease progression.