Part 1 · The disease
What FMF is
Familial Mediterranean fever is the most common inherited autoinflammatory disease 263: short, self-limited attacks of fever with inflammation of the lining of the belly, chest or joints. Pick a population and press play to see how common the gene variants are, and why far fewer people get sick than the variants alone would predict.
Each figure is 1 person in 100. Carrier rates come from different studies that tested different variant panels by different methods, so they are not one comparable series. The predicted figure is a simple estimate: it assumes random partnering, counts only the variants that study tested, and ignores reduced penetrance, so it is not a disease rate.
Why are carriers so common?
Disease variants usually stay rare because they are a burden. FMF variants reached carrier rates of about 1 in 5 in several populations. One explanation is that carrying one copy once helped people survive an infection. Drag through two thousand years.
Schematic model, not a reconstruction: constant selection at the coefficients estimated by Park et al. 2020 (s ≈ 0.077 per generation for M694V and 0.068 for V726A, 25-year generations), each variant starting as one rare copy at its HMM age estimate. The same paper's Gamma method puts the most recent common ancestor further back, about 3,541 years for M694V and 3,372 for V726A, so the start of each curve is the younger of two published estimates. The starting frequency is illustrative. Real selection was probably uneven.
An attack at a glance
How often each site is involved, in the Turkish national registry of 2,838 patients. 264 Tap a bar to see where it is and what it feels like.
Fever and peritonitis together are the classic attack. For what happens hour by hour, with CRP and SAA curves, see An attack, hour by hour.