Which are the causes of Marshall syndrome - PFAPA?

Marshall syndrome is a rare genetic disorder that falls under the umbrella of periodic fever syndromes. It is also known as PFAPA syndrome, which stands for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. This condition typically affects children and is characterized by recurrent episodes of fever, sore throat, mouth ulcers, and swollen lymph nodes in the neck.

The exact cause of Marshall syndrome is not yet fully understood. However, research suggests that it may be caused by a combination of genetic and environmental factors. Let's explore some of the potential causes:

Genetic Factors:

1. Gene Mutations: Marshall syndrome is believed to be caused by mutations in certain genes. One of the genes implicated in this condition is the MEFV gene, which is also associated with another periodic fever syndrome called familial Mediterranean fever (FMF). Mutations in the MEFV gene can lead to abnormal activation of the immune system, resulting in the characteristic symptoms of Marshall syndrome.

2. Autosomal Dominant Inheritance: In some cases, Marshall syndrome may be inherited in an autosomal dominant manner. This means that a child has a 50% chance of inheriting the mutated gene from an affected parent. However, it is important to note that not all individuals with the gene mutation will develop the syndrome, indicating that other factors may also play a role.

Environmental Factors:

1. Infections: It is believed that certain infections may trigger episodes of fever and inflammation in individuals with Marshall syndrome. These infections can include viral, bacterial, or even fungal pathogens. The exact mechanisms by which these infections trigger symptoms are still being investigated.

2. Immune System Dysfunction: Individuals with Marshall syndrome may have an underlying dysfunction in their immune system, which makes them more susceptible to infections and inflammatory responses. This dysfunction may be related to the genetic mutations mentioned earlier, but further research is needed to fully understand the connection.

Other Factors:

1. Age: Marshall syndrome typically presents in early childhood, with symptoms appearing before the age of 5. The exact reason for this age predilection is not known, but it suggests that certain developmental factors may contribute to the onset of the syndrome.

2. Triggers: Some individuals with Marshall syndrome may have specific triggers that lead to the onset of fever episodes. These triggers can vary from person to person and may include factors such as stress, certain foods, or exposure to environmental allergens.

It is important to note that while these factors may contribute to the development of Marshall syndrome, the exact interplay between genetics, environment, and immune system dysfunction is still being studied. Further research is needed to gain a comprehensive understanding of the underlying causes of this rare disorder.