Is TNF Receptor Associated Periodic Syndrome hereditary?

TNF Receptor Associated Periodic Syndrome (TRAPS) is a hereditary autoinflammatory disorder caused by mutations in the TNFRSF1A gene. It follows an autosomal dominant inheritance pattern, meaning an affected parent has a 50% chance of passing the pathogenic variant to each child.

Is TNF Receptor Associated Periodic Syndrome hereditary?

Yes, TNF Receptor Associated Periodic Syndrome is a strictly genetic condition. It is inherited in an autosomal dominant manner, which means that a single copy of the mutated TNFRSF1A gene is sufficient to cause the disease. While most cases are inherited from an affected parent, de novo (spontaneous) mutations can occur, meaning an individual may be the first in their family to be diagnosed with TNF Receptor Associated Periodic Syndrome.

How is TNF Receptor Associated Periodic Syndrome diagnosed genetically?

Genetic testing is the gold standard for confirming a diagnosis of TNF Receptor Associated Periodic Syndrome. Diagnosis involves sequence analysis of the TNFRSF1A gene to identify pathogenic variants. Clinical geneticists recommend testing when a patient presents with recurrent fevers, migratory rashes, and musculoskeletal pain consistent with the syndrome. Because the penetrance of the gene can be incomplete, some individuals may carry the mutation without showing severe symptoms, which makes family screening highly valuable.

What are the implications for family planning?

For families affected by TNF Receptor Associated Periodic Syndrome, genetic counseling is essential to understand reproductive risks and options. Key considerations include:

• Inheritance Risk: Each pregnancy for an affected individual carries a 50% risk of inheriting the TNFRSF1A mutation.


• Prenatal Testing: Options such as chorionic villus sampling (CVS) or amniocentesis are available for those who wish to know the genetic status of a fetus.


• PGT-M: Preimplantation Genetic Testing for Monogenic disorders (PGT-M) can be performed in conjunction with IVF to select embryos that do not carry the specific mutation.


• Genetic Counseling: Counselors help families navigate the emotional and clinical complexities of passing on the condition to future generations.

Next steps

• Consult with a clinical geneticist to discuss targeted TNFRSF1A gene testing.


• Connect with the 4 members of our DiseaseMaps.org community who are currently managing TNF Receptor Associated Periodic Syndrome.


• Speak with a rheumatologist specializing in autoinflammatory diseases to monitor symptoms and potential complications like amyloidosis.

Medical disclaimer: This information is for educational purposes and should not replace professional medical advice, diagnosis, or treatment.

References

• NIH Genetic and Rare Diseases Information Center (GARD): TNF Receptor Associated Periodic Syndrome.


• Orphanet: TNF receptor-associated periodic syndrome (ORPHA:3335).


• OMIM (Online Mendelian Inheritance in Man): TNFRSF1A-ASSOCIATED PERIODIC SYNDROME; TRAPS.


• Autoinflammatory Alliance: Patient resources and clinical updates on TRAPS.