A genetic disorder that makes people unable to feel itch

Question

I know that congenital insensitivity to pain exists and is autosomal recessive. There is a village in Sweden where 40 cases of this rare genetic disease were reported.

I am writing a story with a strange genetic disease called congenital insensitivity to itch. In my story, congenital insensitivity to itch is common in a village inhabited by 600 humans: 30 of them have it.

So, I wonder if my genetic disease is possible or a total fiction. What would be congenital insensitivity to itch's mode of inheritance: autosomal dominant (like Marfan syndrome), autosomal recessive (like cartilage-hair hypoplasia), X-linked dominant (like X-linked pituitary gigantism), or X-linked recessive (like Hunter syndrome)?

If this is autosomal, what chromosome is linked? Chromosome 1 (like Hutchinson-Guilford progeria), chromosome 2 (like Ehlers-Danlos syndrome), chromosome 3 (like retinitis pigmentosa), chromosome 4 (like achondroplasia), chromosome 5 (like Sotos syndrome), chromosome 6 (like hemochromatosis), chromosome 7 (like tritanopia), chromosome 8 (like Werner syndrome), chromosome 9 (like cartilage-hair hypoplasia), chromosome 10 (like type 2 multiple endocrine hyperplasia), chromosome 11 (like sickle-cell anaemia), chromosome 12 (like phenylketonuria), chromosome 13 (like Wilson disease), chromosome 14 (like Krabbe disease), chromosome 15 (like Marfan syndrome), chromosome 16 (like Morquio syndrome), chromosome 17 (like type 1 neurofibromatosis), chromosome 18 (like type-C Niemann-Pick disease), chromosome 19 (like Donohue syndrome), chromosome 20 (like adenosine deaminase deficiency), chromosome 21 (like autoimmune polyendrocrinopathy-candidiasis-ectodermal-dystrophy), or chromosome 22 (like type 2 neurofibromatosis)?

I know I made an extremely long enumeration because the vast majority of the human genome is nuclear and autosomal, sorry.

Answer 1

Sure. A different NTRK mutation could lose itch but keep pain.

Nerve growth factor, pain, itch and inflammation: lessons from congenital insensitivity to pain with anhidrosis

Congenital insensitivity to pain with anhidrosis is a genetic disorder due to loss-of-function mutations in the NTRK1 gene encoding TrkA, a receptor tyrosine kinase for NGF. Since patients with congenital insensitivity to pain with anhidrosis lack NGF-dependent unmyelinated (C-) and thinly myelinated (Aδ-) fibers, and their dermal sweat glands are without innervation, they exhibit no pain, itch, signs of neurogenic inflammation or sympathetic skin responses.

This syndrome (CIPA syndrome) is a loss of function in TRKa which is a factor that promotes growth of certain kinds of nerves. It is autosomally recessive. Persons with a mutant TRKa have no pain and also no itch and are generally developmentally disabled. A described case has no pain but did have itch (and normal mental function) and had a different mutation in TRKa.

If you want it to be realistic, you could just use people with CIPA. Or you could have people that carry a different loss of function mutation in TRKa that affects itch more and pain + sweating less; the inverse of the mentally normal case linked above. There are lots of double recessive people because of inbreeding in this small town.

If you are ok with less realism you could have a gain of function of TRKa. They have pain (lots) and sweat (lots) and maybe they perceive itch as something different. Maybe it is painful. Or maybe it is perceived as "pleasurable touch", which is a less well investigated component of skin sensory abilities. These folks are heterozygotes and so no need for consanguity.

Answer 2

So, I wonder if my genetic disease is possible or a total fiction

Its hard to say, because itching isn't perfectly understood. There are a few different classes of nerve fibre involved, and it seems to be part of the pain reception system, but full understanding is lacking. It is possible that you could only become truly insensitive to itching if you were also insensitive to pain, and I'm assuming that isn't something you really want.

There's a possibility that there are itch-inducing proteins and receptors on nerve cells that are triggered by them. Whether it is possible to malform either or both of those and suppress or reduce the feeling of itching isn't clear, but there is an avenue of exploration there. Chances are that modifications to the genes which ultimately encode those proteins will also have a bunch of other effects too, though. Few genes are convenient on/off switches for a single system and nothing else.

It might be possible to get something similar to being itching insensitive by having some change or damage to the anterolateral system. This system, amongst other things, deals with identifying where painful stimuli are originating and triggering basic responses, like "put down the hot thing" or "scratch the itchy bit". It is possible to conceive of someone who could feel an itchy sensation and identify it as itchy, but not actually care about it at all and have no scratching responses.

What would be congenital insensitivity to itch's mode of inheritance

Because the exact nature of itching isn't very clear, there's no obvious way to disable it without disabling a bunch of other things and as such the nature of the inheritance pattern associated with genetic insensitivity to itching can't be defined.

Pick one you like, that suits your story, and that'll have to do.

Answer 3

It's Plausible and Being Studied

University Hospital of Basel are / have been studying two patients with sensory and autonomic neuropathy. Both are insensitive to pain. They also seem to be insensitive to itch. After a histamine test, most people itch & scratch. These subjects just flatline -- see fig 1 in the link.

For your story, I don't think you really need to get into too many details. You might drop a name in dialogue -- "...remember that study University Hospital of Basel did a while back?" But I wouldn't get mired in the neuroscience. Unless you're an actual neurologist!