Researchers from the Seaver and NY Autism Center of Excellence at New York’s Mount Sinai School of Medicine have developed a new method to detect copy number variants associated with autism spectrum disorders and have also found new chromosomal duplications that can be linked to autism.The study is published in the October 16th BMC Medical Genomics.

279 child with ASDs were screened for micro-duplications and -deletions in regions of the genome that have been connected to other cognitive conditions. The researchers detected several previously known duplications associated with autism, but also some that had not previously been recognized. The approach that psychiatry researcher Joseph Buxbaum and his colleagues used is multiplex ligation-dependent probe amplification, or MLPA which, it’s underlined, is an inexpensive and “efficient method to screen or chromosomal abnormalities,” whether these are large or small duplications.

Here’s a summary of the study from Genome Web:

The researchers screened 279 unrelated children with ASD using four different MLPA panels targeted parts of the genome previously linked to cognitive impairment. The subjects, who were around 8 years old, were not pre-selected based on dysmorphism or cognitive defects, Buxbaum said.

After weeding out copy number variants that were found in healthy controls and validating micro-deletions or -duplications using fluorescence in situ hybridization, quantitative PCR, or direct sequencing, the researchers found that about one to two percent of those with ASD also had a chromosomal abnormality associated with cognitive impairment.

For instance, they found subjects with duplications in a chromosome 15 region known to be involved in Prader-Willi/Angelman syndrome, a region of chromosome 22 that’s linked to DiGeorge syndrome, and a region of the X-chromosome that’s associated with X-linked non-specific mental retardation. The team also detected subjects with a partial duplication in the ASMT gene, which is found in the pseudoautosomal region 1 of sex chromosomes and has been previously linked to ASD.

Although the approach is quick and easy, Buxbaum cautioned, MLPA can’t be used to find new, unknown mutations — a situation that may occur in autism. That means it could miss private mutations that could be caught using array CGH with a dense chip.

In contrast, array CGH is “very expensive and time consuming.”

Buxbaum notes that these findings are mostly significant for an etiological understanding of autism and to starting a child on therapy as soon as possible:

………he emphasized, it would be unrealistic and undesirable to think of applying this sort of test in a prenatal setting, particularly because the individual mutations associated with autism are often incredibly rare, often with a vast range of expressivity. In cases where there is a family-member with a known genetic condition, Buxbaum noted, genetic testing for that specific condition can sometimes be desirable.

“Every time you say genetic testing, some people automatically think of pre-natal testing,” Buxbaum said. “This is more about giving an etiological diagnosis to children with autism.”

Multiplex ligation-dependent probe amplification for genetic screening in autism
spectrum disorders: Efficient identification of known microduplications and
identification of a novel microduplication in ASMT can be read as a PDF file.

Currently, there’s no prenatal genetic test for autism. Long ago (as in “around the time I first started writing this blog”) I referred to such testing as “fighting word“: While some would welcome the notion of knowing that a child-to-be would have a disability, others have been quick to point out the possibility of people choosing to abort a fetus if a disability were detected.

In the October 13th Babble, an online web community for a “new generation of parents,” Karen Dempsey writes about Choosing (a) Life: They said our baby would have Down’s; we said we understood. We had no idea. Having conceived her second child after a year of infertility treatments, Dempsey was concerned that the “risks of amniocentesis outweighed the chances it would detect a problem.” During an ultrasound, the radiologist detected other possible signs of Down Syndrome (echogenic intracardiac focus, or EIF; the size of the baby’s nose). Dempsey and her husband knew they were going to have their baby, no matter what. The article depicts Dempsey’s emotional state and thoughts while awaiting her daughter’s birth:

One sleepless night near the end of my pregnancy, I lay in bed with my heart racing, remembering that tiny star from the ultrasound. Were we kidding ourselves, pretending we could just take things as they came? I couldn’t calm myself, though I was desperate to sleep. I tried relaxing by tightening and releasing the muscles of my body one by one, beginning at my toes. I should pray, I thought. I should pray for her. But what did that mean? She was there, fully formed inside of me. I could feel her knees and elbows, her stubborn round head. I didn’t believe in a prayer that would change her genetic makeup; she had Down syndrome, or she didn’t. And so what would I be asking for, a different baby? I’d already chosen to have this one. I finally found peace, and sleep, with the thought, She is who she is. Already, she is who she is, and she is mine.

Liddy does not have Down’s Syndrome, but she has a number of medical conditions: a heart murmur caused by a congenital heart defect, swollen kidneys, an elevated white blood cell count, severe gastroesophogeal reflux disease. Dempsey writes of what testing could have told her and what it could not have:

An amniocentesis would not have predicted Liddy’s complications, or prepared me for the realities of having a sick child. Caring for Liddy challenged my marriage, my family relationships, my friendships and my mental health — my very way of being in the world. John and I were naïve. We would learn, through Liddy, the awe-inspiring breadth of medicine’s understanding, as well as the frustration and grief of its limitations — and of our own.

There’s no question in my mind that we were going to have Charlie when I was expecting, “whatever” he might have. Dempsey’s experience seems to me a potential harbinger of questions that parents may find themselves facing should more prenatal tests be developed, including these tough questions:

Will medicine suggest that any and every variation from absolute normalcy is pathological?

How can we draw lines between disabling diseases such as severe autism and more mild differences such as Asperger’s, which may give society some of its greatest achievers?

Will parents have complete say over the kind of children they want to bear?

And what sorts of messages will doctors and genetic counselors convey when talking about risks, probabilities and choices that involve not life and death but personality and sociability, genius and geekiness?

Tough questions and big questions. Here’s two perspectives, one from a scientist and another from the father of an autistic daughter.

For myself, I would to some extent have appreciated knowing Charlie’s diagnosis as early as possible. Perhaps it’s from the memory of all my wondering, worries, and confusion during Charlie’s babyhood, when subtle things said “things are different,” but nothing stood too much out, and no one wanted to say “maybe he needs to be evaluated by a specialist.” On the other hand, before there might be such a test, it seems all the more imperative to—like parents of children with Down Syndrome—present a hopeful message out there about autism, with an emphasis on how it’s not a dreadful death sentence, and that we know a lot more and can help a child greatly.

When I tally up all the things that have happened to Jim and Charlie and me since Charlie was diagnosed, it’s a rich harvest of experience, with some really tough and awful times (because society and communities did not know what supports and services to provide him with to thrive) and some so good, you can’t imagine life without them.

Following up on the harvest theme, today is “harvest theme day” at the b5media Health and Wellness channel. Wishing you a day of plenty and of sunshine, and of good times with those who walk with you.

So as you may not, or may, have noticed, there is still some wonkiness going up with this blog. The good folks who handle are matters technological, software-related, and the like, have been working hard to migrate b5media’s blogs over to a new server and all should be well, webpages should load and updates occur, very soon. One (”adverse effect?“) of the server migration has been that the sidebar (to your right) has not been updating with recent posts and recent comments. So if a comment is left on a post written a couple weeks or months ago, unless you’ve decided to sit down and read every single post (which I don’t recommend; some posts are more post-worthy than others), some good comments will go missed. I’ve rounded up a few of them below, with a bit of my own responses, and many many thanks for everyone who reads Autism Vox and lets me know what you think.

Anatasia Hulke was found on Monday afternoon, after she’d been missing from her home since Thursday.Regan commented on a bulletin about educational policy from the National Down Syndrome Society and pointed out a Nova video about autism, genes, and a tale of two mice.

A post about late talking written in July continues to draw comments, including this one from John which argues that autism and other disabilities like dyslexia are currently over-diagnosed.

I would counter, they are being diagnosed more because we understand them more and can better identify them, and this notion of better diagnosis needs to be considered in investigating why the rates of autism in Somali children in Minneapolis have increased (here is a commenter, Ali, on this topic).

A commenter, Mindy, asked another commented about seizure medications, Sensory Processing Disorder in a post on sensible accommodations for sensory issues. A couple of friends have been talking on and off about the possibility of using medication for their children. My son’s been on medication since he was 7 and the decision to use it was not lightly made; the medications’ effects are carefully, continually scrutinized. (We’re going to visit Charlie’s pediatric neurologist on Friday to talk about this and some other things.)

The father of a teenage boy asked this question in a post on talking to oneself:

I’ve noticed my 16 yr old boy pace and talk to himself a few times. He is still a bit uncoordinated and has a tendency to walk looking down instead of his head up or stragit ahead. He has above average grades and excels in Japenese but he is a bit sluggish with physical acitivities. I’m a bit concerned becasue his mother (the ex) suffers from schizophrenia and his older brother devleoped a psychois at about 20 yrs of age but had bad grades and drug use may have contributed. Should I be concerned?

Some things I’d ask: Are the pacing and the looking down and the sluggishness long-time behaviors, or relatively new? Are these things affecting him in school or otherwise; does he generally seem happy and all right with things? If he only talking to himself, or also talking to others? Just some thoughts……

Another commenter, Jim Blair, asked me a question in the midst of a comment, quoted here in full; the original post was on prenatal testing (a topic of particular now because of whose youngest son, Trig, has Down Syndrome:

Kristina Chew says:

“And a life without Charlie is a life that neither I nor my husband Jim can imagine, nor would we want to.”

Hi,

Follow me in a hypothetical thought experiment. Imagine that your Charlie had been born a “perfect child” as seen by most people. Suppose he were to grow up to be–depending on your preference, an all star New York Yankee shortstop or Nobel Prize winning scientist. Call him Charlie II.

Would you then make the above quoted claim?

Now suppose that as the result of prenatal genetic testing Charlie I had been aborted and 6 month later Charlie II conceived. Think you would still choose the Charlie I that was never born to the Charlie II that was never conceived?

Of course not. Because we only know the things that ARE and not the things that might have been had we made different decisions.

I thank Jim Blair for taking the time to write out this thought experiment, though I find him to be a bit presumptive about how I would respond to his question. According to him, had I known via prenatal testing that Charlie (”Charlie I,” in the thought experiment) had autism, I would have chosen to abort him, thus making it possible for the conception and eventual birth of a most hypothetical “Charlie II” who would grow up to be an “all star New York Yankee shortstop or Nobel Prize winning scientist” and who, endowed with such an impressive future, would be a child that people would wish to have, and would indeed even consider to be a, if not the, perfect child.

I hope that Jim Blair keeps reading this blog (especially once the software issues gets resolved), as he will then find out why I know that Charlie is perfect and why there was no never any doubt in anyone’s mind that he, once conceived, would be born, and that whatever prior information Jim and I might have from prenatal genetic testing or other testing, we have always chosen to have him.

Always have, always will.

There is no prenatal genetic test for autism; there has been speculation that, as research into the genetics of autism develops, such a test might be created. Back in June of 2006, a team of doctors at University College Hospital in London—in view of the fact that autism is diagnosed in boys at a much higher rate than in girls—announced that they hoped to develop a test to screen for autism in male embryos for couples with a family history of autism. The test would use Preimplantation Genetic Diagnosis (PGD), which screens embryos by taking a single cell from an early stage embryo; embryos with defective genes are discarded.

But how reliable are genetic and other prenatal tests for gender? Today’s Eye on DNA offers a thoughtful overview of the reliability of gender test kits (that cost $300 and even less) that analyze a mother’s blood for fetal DNA; Dr. Hsien Hsien Lei offers some tips for choosing a reputable genetic testing company and quotes William Saletan in Slate:

Notice how the new transforms the old. What’s old is sex selection: choosing whether to abort your fetus based on whether it’s a boy or a girl. What’s new is the combination of ease, safety, and privacy with which you can now do this deed.

And what’s necessary is to get out the message that life with an autistic child (with mine, at any rate) might just be too good to miss out on.