This would revolve around a system of mutations in various forms. You wouldn't choose the mutation you want, it would be inflicted upon you. But you would have the possibility to get it removed. The mutations would be semi-permanent, sitting somewhere between permanent levels (like in DnD/Pathfinder) and temporary equipment-as-level type systems. This would allow players to switch up gameplay style through having mutations cured/removed but not so easily swapped out as simply changing weapons and armour.
What Forms of Mutations are There? We see mutations generally as affectors giving your player ability score advantages/disadvantages and also physical changes, for example extra limbs or scales. These could come from bacterial or viral infections, fungal spores, parasites, radiation, technological augmentation and nanobot infestations.
Where Do Mutations Come From? We're splitting up mutations between different biomes/dungeons/towns as well as mutations inflicted by certain monsters. Monsters may carry diseases with them infecting players on touch or when swallowed/sprayed with blood. Similarly, certain foods, water or merely spores in the air will mutate players when they are susceptible, for example due to wounds or illness.
Benefits/Drawbacks. This is really just personal preference but I've never really enjoyed straight up buffs or handicaps in games. I like my items (especially magical ones) to be like monkey paws. There benefits should come with strings attached. Some mutations will differ from this but in general they'll be a balance of benefits/drawbacks, that way it'll test players and force them to change up their playstyle in reaction to new mutations instead of merely organizing them into keep and discard piles next time they find medicine or a surgeon. Which brings us to...
How Are Mutations Removed? Mutations will be removable by certain surgeons, witchdoctors, clerics, pharmacists and other dubious jungle-dwelling inhabitants with spare scalpels. Some mutations are surface deep, extra hair and skin or growths, others affect the deep organs. These come at a much greater risk when being removed. The correct tools, salves and ointments would help offset this danger. Each type of mutation (e.g. fungal, viral, parasite) would be removed differently/at different cost.
What Do Mutations Cost? Other than obvious drawbacks like ability score or encumberment loses, multiple mutations would come with nutrition costs, forcing your player to eat more often to stay alive. This'll make those deep dungeon dives even more difficult and rations more important.
|This guy has several.|
Sun Blight. Waxy welts appear across your face, neck and back. You no longer burn in the harsh sun but you're more likely to bleed out when struck.
Nail Skin. For 1d6 days you're stuck in agony as nail-like extrusions grow from the skin around your shoulders, knees and wrists (like they do from the ends of your fingers) but overlapping as if into plate armour. For 1d6 days you're more likely to fumble when attacking, running or jumping. After that you now have a higher natural armour score around your shoulders. knees and wrists.
Sac Pox. When submerged in water, small sacks lining your skin inflate causing you to float. You now can float with ease on water but cannot dive.
Wood Eye. Your eyes harden and your sclera changes from milky white to a dark brown. You can no longer look left or right but your vision is much greater than before. (+ to Wis/Perception)
Gorgonbane. Your palms are as cool as anyone else's but stone melts under your touch. Wood, paper, glass, no other material is affected. Just stone.
Desertscalp. You awake hairless atop your head, but your body hair begins to grow prolifically and in places it never did before.
Tremour. Muscle growth is as if on steroids. Your legs bulk out in days and your ability to run is greatly increased. But you shake uncontrollably. Accuracy with a ranged weapon is almost impossible.
Curlfinger. Unless constantly worked at your fingers begin to seize-up into a tight fist. If you grip anything for longer than 2d20 minutes your cannot release it again.
Krykkit. Whenever motionless your create a chirping noise.
Bouldershoulder. The muscles in your shoulder grow an extra 3d100 cm in diameter (+ Str). Your swing may be faster and harder now but you struggle to wear any non-custom made armour and have difficulty sleeping at night.