Sporadic and Heritable Autism
March 16, 2007 by Kristina Chew, PhD
Filed under Genetics, Health, Science, Treatment
Autism is understood more and more to be a genetic disorder; to many, the word “genetic” implies that autism is inherited from one’s parents. A new study focuses on de novo (spontaneous; present in the child but not in his or her parents) mutations rather than on inherited mutations. Research published in the March 16th Science magazine has “found a distinction between heritable and sporadic forms of the disease,” as a press release from Cold Spring Harbor Laboratory announced today.
“Sporadic” cases of autism are those in which there is no history of autism in the family. Using high-resolution method for analyzing DNA called microarray technology, the researchers found that many autistic children have spontaneous (de novo) copy number mutations in their DNA, and that these gene mutations occur more often in cases of sporadic autism rather than in familial (heritable) cases or in children who do not have autism. 264 families participated in the study. An article in the March 15th The Scientist provides more details:
The study found that 10% of children (12 out of 118) with sporadic autism had de novo copy number variations, whereas only 1% of controls (2 out of 196), who had no history of autism, showed CNVs. Among families with multiple autistic children, only 2% (2 out of 77) autistic children showed differences in copy number from their parents.
The researchers plan to screen more than 2000 families over the next three years. Most genetic studies of autism have been of families who have multiple autistic children; scientist Jonathan Sebat notes that “’sporadic autism is genetically distinct from the type that runs in families’” and therefore is to be treated differently.
The results strengthen the scientific basis for using microarray technology for diagnostic testing. Methods for detecting spontaneous mutations will provide important information for children with autism and their parents. This information could help to determine the risk of having a second child with autism, and the knowledge of which genes are involved may lead to the development of new therapies.
My understanding of this study on gene mutations in autistic children is that my son Charlie would qualify as a case of “sporadic.” He is our only child with autism, and also our only child. I am wondering if relatives on the autism spectrum who are not part of one’s immediate family might also be considered: Does having an autistic cousin, for instance, mean that one’s autism is still completely sporadic? What if families were screened in which there was one autistic child and an autistic parent (see Autism Diva on the BAP or broader autism phenotype, “the condition of having just a touch’ of autism that is frequently found in the parents and other close relatives of autistic kids”). Again, Charlie is our only child; we chose only to have Charlie, so the possibility remains that Charlie could have had an autistic sibling.
The researchers note that their work may influence diagnostic testing and also treatments for autism. This research was primarily funded by the Simons Foundation, whose 2007 Autism Research Initiative notes that its mission is to “understand the causes of autism and thereby improve the diagnosis, treatment, and prevention of this and related developmental disorders.” And thinking it over tonight—as I am preparing a presentation on teaching autistic college students and Charlie ran excitedly through the house when his teacher came for a visit, cried and cried when I asked him to wait till the garbage can was full before taking it out, and asked for “Sesame Street book” after spotting the program for a musical show he saw last year tucked behind a shelf—reflecting on all this, I really cannot imagine a world without Charlie, without Charlie as he is today.
However Charlie came to be—whatever mutations, deletions, variations of genes brought him into being—it is a good thing that they did.
Jeff Stimpson
Jill Cornfield
“However Charlie came to be-whatever mutations, deletions, variations of genes brought him into being- it is a good thing that they did.”
I heartily agree with you Kristina!
I wouldn’t change my little boy for the world!
I just love him to bits.
He is who he is.
And I will always be eternally grateful to God for him..
WE as a family have learnt so much from Mark!
While I sure some sporadic cases exist, I’d like to know those kids opinions on whether their parents have autistic traits or not.
I’m wondering what they mean by stating that these different kinds of autism should be “treated” differently… My immediate reaction was that different genetic causes won’t/shouldn’t determine which therapy allows a child/person to learn to function their best, but then I realised that they must be talking about possible gene therapies. It really does put a different spin on the word “treatment”, doesn’t it?
Are there other differences between the ’sporadic’ cases and ‘heritable’ cases - other medical concerns I wonder. Not everthing is hereditary.
in terms of whether someone has ‘undiagnosed autistic traits’ EVERYONE has a little bit of autism in them.
Its being overdiagnosed without addressing underlying medical concerns for some people. ‘ADHD’ and ‘ADD’ are part of the chain even though some people would dispute this. (like parents of kids that maybe carried an initial autism label that ‘came out of it’ and got a new diagnosis. )
The stigma is still so prevelent, sadly, and thats what needs to change.
The premise of the movie ‘Gattaca’ is sort of coming true. But the tagline for the movie was “There is no gene for the human spirit”
Now the next question to ask is…
What if sporadic mutation is how the first autistics came into being thousands of years ago? Doesn’t the fact that it survived and was able to breed into something heritable a sign that as a whole, autistics are a good thing?
If you look at the theory of survival of the fittest, if being autistic was only a negative and was of no good to the group, tribe, family, culture then the early autistics would not have lived long enough to have children of their own, and heritable autism would have not started.
I would hope that the proof that there is autism genes that have been around passing from parent to child AND it’s still showing up as a sporadic mutation shows that there’s something important in that mutation that was needed for humans to advance in the past, that may even still be needed to advance in the future, and thereby show groups that want to cure us that maybe it’s not such a good idea to even try.
I also love my son the way he is, and I wouldn’t change him for anything. But on top of that I like myself the way I am and do not want to be made into someone else to make others happy. To quote a famous sailor “I am what I am.”
With regard to BAP, there is a real risk of our attempts to understand autism leading us to see as diseased that which is merely a characteristic. There is a risk of us seeing all the geeky/nerdy people and everyone who has an undistinguished career in science, who we happen to find in our extended families, as proof a genetic disorder. That’s kind of limiting and sad. Who is to say that the geeky/nerdy range of variation is the disorder and salesman/football player end is healthy? There are situations in which we could just as well argue the opposite. Of course, either argument comes down to eugenics, and while there are many proponents of eugenics in the autism research fields, it is of no utility in dealing with people who have already been born. (By the way, I am fully aware that the Autism Diva herself is not a proponent of eugenics or the ways of thinking that I am warning of.)
There is also something potentially misleading in a simplistic analysis of this research on on CNVs. The article presents it as evidence of a causal relationship between a discrete medical condition called autism and genetic mutations. At first glance, comparing 10% in the test group with 1% in the control group seems highly significant. Certainly it fits the technical definition of significance. But when you are trying prove causation, 10% is a very low number. It leaves 90% unaccounted for by one’s model.
The article is also guilty of a sort of petitio principii fallacy. Its claim to the effect that autism is a genetic disorder is only supported if we assume that autism is a discrete disorder in the first place and that their test group is made up of people who all suffer from this single disorder. If you restate the findings as, “When compared with people who act normal, we measured more overall CNVs in 10% of people who act weird,” you wouldn’t be saying much.
CNVs are assumed to be associated with abnormal levels of certain proteins (simplistically, more copies mean more protein and fewer copies means less protein). Essentially all biological variation comes down to differing levels of proteins in various places. For example, Johny and Jane may both have trouble sleeping. Johny may have low levels of a protein that helps people fall asleep. Jane may over express a protein that helps people wake up. If you analyze their DNA, you will probably find that both Johny and Jane have CNVs, but it is in no way true that Johny and Jane both suffer from the same discrete genetic disorder.
I should point out that I actually do imagine that autism is a phenotypical expression of a relatively discrete genetic variation. I just don’t think the work presented in the article does anything to support my view.
“EVERYONE has a little bit of autism in them.”
What I was getting at is that, even if it’s not official, almost everyone I’ve spoken to says they can see their autism in inherited. I know about the theoretical 100 point trait scale, where say, someone who’s autistic is 70 and up, and a neurotypical would be somewhere below that. The typical neurotypical would be, say 20 to 30. But adult autistics see a higher than average neurotypical point scale in their parents.
VAB: Thank you so much for your analysis; lacking the science background to really analyze these kinds of findings, I try to respond as thoughtfully as I can, and to also include my gut reactions as a parent. I really, really, really appreciate your views on this article.
I continue to be puzzled by the resistance of some in viewing autism as genetic. My husband is always glad to say, “Charlie’s like us.”
Manju says:
I agree with VAB that the study assumes autism to be genetic disorder and that autism is only a charecteristic manifested by a more complex cause and not entirely genetic, because what would explain the non genetic diseases associated with autism like presentation like congenital rubella syndrome. It also runs in families with autoimmune disorders, not necessarily sporadic genetic disorders. I think this is ’survival of fittest’ that is, the these kids need to be unconnected socially as the world is heading into such an era where the people who are depedent on materialist world for work and pleasure survive well. It seems true we moved from using our ears for listenig radio to using eyes to watch television. The autistic trait we developed is passed on to our next generation be it an autistics’ strong feature.
In today’s world of computers and video games and television entertainment which child has the inclination to go and improve social skill. Even responding to parents’ call becomes a rarerity as the child is constantly at these gadgets. The evolution is preparing the future generation for this material world and we all will be extinct and might as well be compared to dinosaurs for talking about social interaction.
Usal wrote:
Agree on both points (and agreeing with the sailor too–we’ve a picture of Charlie and the statue of him in his creator’s home town of Chester, IL).
Haven’t seen Gattaca, yet….
Kristina said:
I think it’s our community’s analogue to a well-known archetype in the gay community: the virulent homophobe who is the way he (almost always a he) is because deep down inside he’s afraid he might just be a little gay himself…
Lately I’ve been thinking about my future children. I turn twenty on 4-4, so I’ve been looking back at my teen years a lot, thinking about adulthood which still (thankfully) looms ahead.
I’m really worried. I know that there’s a high possibility that any child I have will have bad allergies, hyperthyroidism, even a higher chance of substance abuse (at least stretching back to great-grandparents on both sides, but especially my maternal lineage). But I worry *most* about autism.
It makes me feel really selfish, but I’m aware enough to realize that I’ve got problems socializing and empathizing with my peer group; I was a precocious child who didn’t relate well to others, couldn’t understand their fads.
Knowing these things about myself, I make myself work them through — I work on making eye contact instead of focusing on mouths, I go to large gatherings when I’d really rather go home and read a book or do a Sudoku puzzle. I know that I’m normal, but I have a hyperawareness of my own social inabilities due, I think, to Scotty.
My brother’s nonverbal, and he’ll have to live with a family member his entire life. My grandparents are in ill health; within the next decade, decade & a half, I think my sister & I will have Scotty for ourselves. How’re we going to do that? We’re still young kids, so it’s almost a distant future to us yet. My mother couldn’t take him, our younger brother & sister didn’t grow up with us. We’ll be alone in trying to help him.
It’s scary, but it’s more scary to think that, as a parent, I’d have to worry about those things. It’s scary to think that I’d have a baby who’d get the same teasing, have a little boy who couldn’t go to church because he wouldn’t be able to sit through mass, a frustrated little girl who couldn’t tell us what was bothering her.
Or even a kid who had the same trouble socializing that I did — it was horrible, absolute misery. I didn’t like what they liked, I didn’t speak how they spoke (I like the sound of words, and as a child, it was precise speaking, not slang, that appealed to me), I was rude without meaning to be, I didn’t consider their feelings, and I corrected everybody, including teachers.
On one level, I think I’m more prepared for it than someone who doesn’t have an autistic sibling; on another, I worry that — initially at least — I’ll have more resentment for the situation than someone with a ‘clean slate.’
Like I said, it makes me feel mean and selfish, but it’s a long way off.
John Timmer at Ars Technica has written a good summary of this study.
My Brother has two daughters. One contracted memingitis soon after birth and suffered mental retardation as a result. The second is currently being ‘tested’ for Autism. There are no other family members that show signs of Autism in our side of the family, however, my brothers wife has family that have been diagnosed as such.
My wife and I are currently considering having children, whats the probability that we could have an autistic child? Is there any way to test for it? I may be being paranoid but its a concern I have. Any advice would be appreciated.