Which are the causes of Hereditary Leiomyomatosis and Renal Cell Carcinoma?

Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) is a rare genetic condition that is caused by mutations in the FH gene. This gene provides instructions for producing an enzyme called fumarate hydratase, which is involved in the energy production process within cells.

1. Inherited Mutations: The primary cause of HLRCC is the inheritance of a mutated FH gene from one or both parents. This condition follows an autosomal dominant pattern, meaning that a person with a single copy of the mutated gene has a 50% chance of passing it on to their children. Individuals who inherit a mutated FH gene from both parents are more severely affected.

2. FH Gene Mutations: Mutations in the FH gene disrupt the normal functioning of fumarate hydratase. As a result, there is an accumulation of fumarate, a byproduct of cellular metabolism, within the affected cells. This buildup of fumarate leads to the development of leiomyomas, which are benign smooth muscle tumors commonly found in the skin and uterus of individuals with HLRCC.

3. Increased Cancer Risk: HLRCC also predisposes individuals to the development of renal cell carcinoma (RCC), a type of kidney cancer. The exact mechanism by which FH gene mutations contribute to RCC is not fully understood. However, it is believed that the accumulation of fumarate in kidney cells may trigger the growth of cancerous tumors.

4. Environmental Factors: While FH gene mutations are the primary cause of HLRCC, certain environmental factors may influence the development and progression of RCC. These factors include exposure to certain chemicals, smoking, obesity, and high blood pressure. It is important to note that these factors alone are not sufficient to cause HLRCC, but they may contribute to the overall risk of developing RCC in individuals with the condition.

5. Genetic Counseling: Given the hereditary nature of HLRCC, individuals with a family history of the condition or those who have been diagnosed with HLRCC should consider genetic counseling. Genetic counselors can provide information about the risks, inheritance pattern, and available testing options for HLRCC. They can also offer guidance on family planning and preventive measures to manage the associated health risks.