My first thought, and I sure you have had this thought too, is that if ME/CFS patients are born with some sort of minor physical spinal abnormality, as manifested by a sacral dimple, perhaps this could be a predisposing factor to developing ME/CFS later in life.
For example, maybe the spinal abnormality reduces cerebrospinal fluid (CSF) flow, and so when you catch a virus which infects the central nervous system (CNS), perhaps that makes it harder for the immune system to control and clear the virus from the CNS (as immune cells in the CNS are carried along by the CSF).
In addition, we know that spinal cord injury can result in reduced natural killer (NK) cell cytotoxicity, reduced NK number, and upregulation of proinflammatory Toll-like receptors. So if there are some subtle abnormalities in the spinal cord at birth, then perhaps these might cause some subtle weaknesses in the immune response, and/or a tendency to excessive proinflammatory responses, again making it harder to control and clear viruses.
Of course, all pure speculation
This spinal abnormality may not necessarily be genetic, it may just be something that arises as a result of the conditions of gestation.
So it may not show up in a genetic study, but nevertheless, ME/CFS patients might be predisposed at birth to developing ME/CFS later in life, once they catch a virus which can infect the central nervous system, which
may be the immune weak spot in their body.
Hip....Many years ago my neurologist and I were having a discussion. I'm one of the lucky ones, he's deeply invested in his patients. He said something I've always remembered: "Most of his patients with spinal cord problems, went on to develop ME/CFS/FM (at the time). This was years and years ago and he was particularly perceptive. Interesting as his wife had a lot of the same problems I had and she now has unremitting Parkinson's, which was misdiagnosed by other neurologists for years. She's very ill today, as most of you would know.
I think he's right, and whether the causes are from gestation (which mine are...scoliosis, then Syringomyelia, then Arnold-Chiari Malformation...as medicine allowed them to be discovered). I also have Tethered Cord Syndrome and since I couldn't survive surgery at this late date (also have cardiac problems and a form of Encelphalitis), I'm hoping that I'll manage the tethered cord until I die.
What's interesting is that my mother was a British war bride, and of course rationing was commonly done in those years. Who knows, perhaps she didn't like a lot of foods, too. I'm the only one, the first in a huge family of 9 children (most dead now). I never told anyone in my family, except one sister, long after my mother had died. I didn't want her feeling responsible for something she couldn't help. Later on it was found that ashortage of folic acid (a B-vitamin) was found in a no. of children who died here in S. TX of anencephaly (absence of the brain). Now Syringomyelia and Spina-Bifida are closely linked, that was my first clue. Also, later research has found a link between l. sided scoliosis at a very young age...I started wearing full body casts between 3 & 4 and alternated between braces and casts for the remainder of my childhood years. My mother, thankfully, didn't believe in coddling children, so I did a lot of walking and you know what that means if you're British. It's not that she didn't care, quite the opposite, at some point you had to make it on your own. Best thing that could have happened to me. I continued it for the rest of my life, until 3 rounds of shingles took me out for over a year about 7 or 8 years ago (there is a wonderful vaccine available today. Check your pharmacy. You'll probably have to go on a waiting list for the serum and then it's given in 2 vaccinations...worthwhile, trust me). The old one was only 50% effective and this is between 90 & 95%. You have to be a certain age before getting it. I've had shingles 4 times and never, ever want them again. Anyway, perhaps this info will help someone else. Have your surgeries while you're young enough to recover without extra energy. Lenora.