SHANK3 mutation, 22q13 deletion. I had a chance to briefly meet a child with this rare condition today.
Prevalence rate is 1/8,000 ~ 1/15,000 (according to https://www.pmsf.org/about_pms/), so definitely below the range of what's "normal" as given by the Square Root Law, which I typically take at a value of 1/1,000 (assuming a human tribe size of one million). It's always exciting to be meeting people at this level of rarity.
So I read a bit about SHANK3 gene and its function. It seems its function affects mostly at the synapses.
Autism, as I have discussed many times before, it's a renormalization phenomenon, where, instead of single neurons, clusters of neurons behave like coherent units of interaction. That means strong coupling between neurons. So far, I see at least three mechanisms that can trigger renormalization:
(a) More synaptic connections, more dendrites
(b) Stronger synaptic connections
(c) Myelination leakage
Hypothyroidism (e.g. cretinism) and MS (Multiple Scelerosis) belong to category (c). Phelan-McDermid Syndrome should probably belong to category (b).
https://www.pmsf.org/about_pms/medical-issues/
Macrocephaly: The head may be large due to an unidentified cause or due to a known cause, such as enlarged ventricles. Macrocephaly has been reported in about 25% of individuals with the Syndrome.
Microcephaly: This means that the head is small for age and is more common in individuals with short stature. Microcephaly occurs in fewer than 15% of individuals with the Syndrome.
So, I don't think there is evidence for macrocephaly, hence it doesn't look like (a). I certainly did not see a big head in the child I met today, nor in most of the online photos.
Given all the typical characteristics of PMS (Phelan-McDermid Syndrome), I think it does belong to the generic group of autism. I know that it's probably considered as a more "severe" form of autism, whatever that means, but I feel more positive than how I feel about the case of category (c). I have no clue how to approach children with myelination problems. But category (b) belongs to the classical type of autism. Sure, there might be issues coming from epilepsy (and thus shortage of working memory), but that's a known devil. This condition is so rare, and frankly research only started recently, that I have not been able to find details about things like marriage and second generation.
What all this seems to suggest is, category (b) might be responsible for pro-video type of autism, where brain circuits tend to loop around and form more vortons than conceptons.
Life is never boring.
09 Feb 2020, 2:03 am
