Which are the causes of Singleton Merten syndrome?

Singleton Merten syndrome (SMS) is a rare genetic disorder that affects multiple systems in the body. It is characterized by a combination of dental abnormalities, skeletal abnormalities, and progressive calcification of the aorta and heart valves. The exact cause of SMS is not yet fully understood, but it is believed to be caused by mutations in certain genes.

Genetic Mutations: The primary cause of Singleton Merten syndrome is thought to be genetic mutations. Researchers have identified mutations in two genes that are associated with SMS: IFIH1 and DDX58. These genes play a role in the body's immune response and are involved in regulating the production of interferons, which are proteins that help fight off viral infections. Mutations in these genes can disrupt the normal functioning of the immune system and lead to the development of SMS.

Autosomal Dominant Inheritance: Singleton Merten syndrome is inherited in an autosomal dominant manner, which means that a person only needs to inherit one copy of the mutated gene from either parent to develop the condition. In some cases, the genetic mutation occurs spontaneously, without being inherited from a parent.

Variable Expressivity: The symptoms and severity of SMS can vary widely among affected individuals, even within the same family. This phenomenon is known as variable expressivity. It is believed that other genetic and environmental factors may influence the expression of the mutated genes and contribute to the variability in symptoms.

Other Factors: While genetic mutations are the primary cause of Singleton Merten syndrome, there may be other factors that contribute to the development and progression of the disorder. These factors could include environmental influences, epigenetic modifications, or additional genetic variations that interact with the primary mutations.

Overall, Singleton Merten syndrome is a complex genetic disorder with multiple potential causes. Ongoing research is focused on further understanding the underlying mechanisms and identifying additional genes or factors that may be involved. This knowledge is crucial for developing targeted treatments and interventions to improve the quality of life for individuals affected by SMS.