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The primary cause of hyperpigmentation in Peutz-Jeghers syndrome is a genetic mutation. This syndrome is a hereditary condition caused by mutations in the STK11 gene, which is responsible for regulating cell growth and metabolism. The disruption in this regulatory function leads to the characteristic pigmented spots, often seen on the mucous membranes and skin, as well as the development of hamartomatous polyps in the gastrointestinal tract.

The hyperpigmentation arises due to the increased melanin production by melanocytes, which is linked to the genetic factors associated with Peutz-Jeghers syndrome. Understanding that this is a genetic condition highlights the significance of hereditary factors in medical conditions, particularly the mechanisms of how genetic mutations can lead to visible clinical manifestations. This contrasts with environmental factors, vitamin deficiencies, or hormonal changes, which do not play a central role in the hyperpigmentation observed in this specific syndrome. Thus, identifying genetic mutation as the cause provides insight into the underlying biology of the disease.