A Rubric for Genetic Diagnosis of Autism
February 7, 2008 by Kristina Chew, PhD
Filed under Health
The previous post considered a physiological marker for autism that draws on research on the brain responses of adolescents with Asperger Syndrome playing an interactive game. Drs. G. Bradley Schafer of University of Nebraska and Nancy J. Mendelsohn of Children’s Hospitals and Clinics of Minnesota have published an article in the January issue of Genetics in Medicine that outlines a three-tiered “practical, stepwise approach” to the genetic diagnosis of autism that will ” a specific genetic diagnosis in approximately 40 percent of patients with autism-spectrum disorders.” Medical News Today provides an overview (my emphases added):
The first tier of genetic evaluation includes tests that should be performed in nearly all children with no obvious cause of autism. For example, chromosome tests may identify fragile X syndrome a common cause of inherited mental impairment that may be accompanied by autistic symptoms. Testing for certain metabolic disorders or for rubella infection may pinpoint a specific cause of autism. If one of these causes is identified, no further genetic testing is needed, and patient/family counseling can begin.
If not, testing enters the second tier, including tests for specific gene mutations known to cause autism. The choice of tests may be guided by certain clinical characteristics. For example, autism in girls has been linked to mutations of a gene called MECP, while autism accompanied by abnormal head size may be related to mutations of the PTEN gene.
If necessary, testing proceeds to the third tier, possibly including a magnetic resonance imagine (MRI) scan of the brain. (Some doctors may recommend MRI scanning earlier in the testing process.) Even if the MRI scan doesn’t show any specific cause of autism, it may still provide useful information for doctors and parents. Tests for other possible genetic causes may also be done, although the value of these tests is so far unclear.
Evaluation by a professional trained in the diagnosis of autism needs to be carried out prior to genetic diagnosis, the study emphasizes.
My son received both the first and third tiers of the proposed genetic diagnosis, though not in any systematic order. He was tested for Fragile X at the time that he was being evaluated for developmental and speech delays back in July of 1999, and he has had two MRIs (which revealed that he has more white matter in the same parts of his brain as do other autistic persons). The truth of the matter is, by the time he was diagnosed, we knew very well that he had autism based on his lack of play skills, no language or communicative skills, and other behaviors as outlined in the DSM-IV. And at that point, getting the diagnosis was crucial in helping us to start to think about how to help Charlie, and this post by the mother of a girl named Maizie says why, and powerfully.
Good Idea, but poor specific guidance given.
Tier 1 speaks about chromosome tests, but not which ones, and certain (but unenumerated)metabolic disorders.
Tier 2 and 3 also have similar vague language. This would not be an A+ paper if I were grading it.
Patrick,
Is that your conclusion from the text of the published paper or from this press release?
It might be more clear whether the paper itself gives more specific direction. Unfortunately our University library doesn’t have a contract for this journal, otherwise I’d check.
Schaefer, B.G, Menelsohn, N.J. (2008). Genetics evaluation for the etiologic diagnosis of autism spectrum disorders. Genetics in Medicine. 10(1):4-12, January 2008.
A more methodical stepwise process would be useful.
Ours was
Speech therapy–didn’t help
Multidisciplinary screen–diagnosis ASD/MR
then EEG for Kleffner-Landau–nope
then time elapses
then test for Rett’s and Fragile X–nope
then time elapses
then test for metabolic disorders–nope
So on that basis, it was all out of order. If Eleanor had had a genuine metabolic disorder, based on the time it took to get to it, she would have been in bad shape. If she had had Rett’s or Fragile X, the original diagnosis would have been wrong.
That may have been a particular FUBAR but my understanding is that it wasn’t too out of line as the process went in our place at that time.
The only thing that seems a little odd, and maybe it’s because I don’t know the full rationale is,
“Evaluation by a professional trained in the diagnosis of autism needs to be carried out prior to genetic diagnosis, the study emphasizes.”
There’s probably a detail, but that seems to put the cart back before the horse.
What I found interesting about this study is that, in rather piecemeal fashion, Charlie had a number of the tests listed. Indeed, the clinic where he was diagnosed (at the Minneapolis Children’s Hospital) gave us the impression that these tests were somewhat routine.
Well, we are in the boonies so the process was not only piecemeal but somewhat random in sequence in an “oh yeah” fashion. So I think the idea of a sequential rubric to be useful.
I asked about the MRI but that was reserved for those with seizures.
Thanks for posting about this.
Regan, I went to (and read) the Genetics in Medicine article linked in the main part of the post. Whether that is the complete paper or not, I am not sure.
Thanks Patrick.
I could be wrong but I think that’s a news release.
The paper itself is 8 pages long and I was interested in the specifics of the recommendations. But unfortunately, no institutional contract…so maybe it’ll show up on PubMed fulltext someday.
Schaefer, B.G, Menelsohn, N.J. (2008). Genetics evaluation for the etiologic diagnosis of autism spectrum disorders. Genetics in Medicine. 10(1):4-12, January 2008.
http://www.geneticsinmedicine.org/pt/re/gim/abstract.00125817-200801000-00002.htm
I was quoting from a news release and cited the website of the American College of Medical Genetics. (I think you have sign up for access to the site’s content.) One hopes that the ACMG might publicize guidelines about how to use such criteria for genetic diagnosis, with full acknowledgement of the ethical issues.