Congenital insensitivity to pain is a rare but well-known condition. It also has an obscure variation that seems minor, but is incredibly deadly. It prevents people from sweating.
People with congenital insensitivity to pain (CIP) are not as lucky as you might think. They can burn or cut themselves badly before they notice anything's wrong. They can accidentally chew through their own lips. Just as a bonus, many don't have a sense of smell. But there's an even more frightening condition in the same family of disorders as CIP that includes anhidrosis, or the inability to sweat.
Once the temperature hits 80, just being in a non-air-conditioned room can be fatal for people with anhidrosis. Any kind of exercise is out, including swimming. And avoiding activities or temperatures that make people sweat isn't enough. There are still viruses and infections to contend with - both made even more dangerous because people who can't feel pain often don't know they're sick or have an infection. The body's way to fight infection of this kind is with fever, but fevers make people sweat. Those with congenital insensitivity to pain with anhidrosis (CIPA), don't know they're over-heating until they collapse or have a seizure due their own high body temperature.
The condition is genetic. It's a mutation of the neurotrophic tyrosine kinase receptor gene, a receptor for a nerve growth factor. If the receptor doesn't grow right, the nerve growth factor can't bind to anything and the nerves aren't properly developed. CIPA is autosomal recessive, meaning it needs two versions of the same defective gene to express itself. Both parents can be totally unaware that they have a single recessive version until they have a child with CIPA.
The condition is serious at every age, but especially in childhood. About half of CIPA children die young due to simple over-heating. Many others get nerve or brain damage from high, prolonged fevers. The only real remedy is avoiding the double recessive genes in the first place. People with a family history of CIPA are often advised to go through a genetic screening before they have kids.