Definition
Actin is an essential component of the cell, enabling it to organize its shape and contents (known as the cytoskeleton), multiply and interact with its environment.
Autoinflammatory diseases linked to mutations in CDC42 belong to the family of autoinflammatory actinopathies.
These diseases are linked to a defect in the regulation of actin cytoskeleton dynamics, in which the CDC42 protein plays a key role.
Epidemiology
These are rare genetic diseases, with just under 20 patients described worldwide to date.
They are cosmopolitan diseases, meaning that they are found all over the world.
These diseases most often begin at birth, with diagnosis often delayed due to their rarity.
Transmission is autosomal dominant, meaning that a single mutation is enough to cause the disease. To date, there are no data on fertility in these diseases. It is essential to consult a specialist to assess the risk of transmission to offspring.
Genetic
Various mutations have been described to date in the CDC42 gene. This list is growing every year, thanks to advances in research and genetics. These different mutations have different effects on the CDC42 protein, disorganizing the cell's actin network and preventing it from functioning properly, leading to severe inflammation.
Clinical
These diseases begin in the neonatal period, with high fever associated with severe rash, digestive disorders (pain, abdominal pain, diarrhea), and reduced blood cell levels, particularly platelets. Liver inflammation has been observed in some patients.
Episodes of very high fever, known as macrophagic activation syndrome, can be life-threatening.
Around half of patients have more infections (known as primary immune deficiency).
Diagnostic
Diagnosis of the disease is genetic. It is diagnosed by a blood test. The referring physician may offer family members a consultation to identify other people with the disease.
There is no indication for genetic testing in people with no symptoms.
Evolution
These are severe diseases with a high degree of inflammation.
They have only recently been described, and there is still little experience of their evolution and long-term risks, particularly in the case of renal amyloidosis.
It is therefore advisable to consult your specialist on a regular basis to ensure appropriate follow-up and monitoring.
Treatment
Patients require specialized management and regular clinical and biological follow-up to monitor inflammation in the blood.
To date, there is no cure.
Some patients may benefit from a bone marrow transplant in the case of very severe manifestations.
Patients with severe inflammatory manifestations will also require specific treatments, some of which may be prescribed orally, others by injection under the skin or by intravenous infusion.
Supportive treatments may also be required: some patients will need transfusions if platelets or red blood cells are low, while others will need specific treatments to reduce the risk of infection if they are more susceptible.