DNA and the Diagnosis of Rare Genetic Disorders (Not Autism)
December 28, 2007 by Kristina Chew, PhD
Filed under Health
While 2007 saw the publication of new research into the genetics of autism, scientists do not yet know what combination of genes—some 30 to 100 have been pointed to—-are involved. The December 28th New York Times profiles children and their families who are in something of the opposite situation. Through newly available DNA testing, some families—-like those of 14-year-old Samantha Napier and 4-year-old Taygen Lane, and of Noa Ospenson, and of Jackson Dopp—have found out that their children have extremely rare genetic disorders resulting from a minute chromosonal aberration. Samantha and Taygen are among six children with the diagnosis “16p11.2.” Some 100 families have children like Noa who are “22q13.” Jackson, who was given a diagnosis of autism this February, has been found to have “7q11.23,” along with 11 other children in the world.
When [geneticist] Dr. [Alan] Rope called to say that there was an extra stretch of DNA in the middle of Jackson’s seventh chromosome, the Dopps rejoiced. His oddness was not the result of bad parenting. Nor was he just a little “off,” as so many people had suggested. Perhaps, Ms. Dopp dared to fantasize, there would one day be a cure for her son. At least now they knew where to look.
But as the Dopps began to tell friends and family members about the source of Jackson’s disabilities, they grew frustrated.
“You say autism, or Down syndrome, and people know somebody,” said Ms. Dopp, who stays home with Jackson and his three siblings. “When you try to explain 7q to people and they barely know what a chromosome is, it’s hard.”
And Dr. Rope had little to offer by way of practical information.
“He said Jackson was the only one he had ever seen,” Ms. Dopp told her husband.
Although they had shied from autism support groups, now they yearned for somewhere to fit in. Finally, Ms. Dopp called an acquaintance whose child had Down syndrome. She had heard of an organization in Britain called Unique that seeks to link families with rare chromosomal disorders.
Ms. Dopp immediately sent away for the registration material. In the packet she received were the e-mail addresses of six other 7q11.23 families.
Jackson, she learned, was one of 11 known children in the world with the DNA duplication. The Dopps were the only one of those families in Utah. She wanted to meet them all. But for now, there was e-mail.
“We have seen occupational therapists, physical therapists, geneticists, speech therapists, neurology, cardiology and eye doctors,” Ms. Dopp wrote. “Have you found certain therapies that work better than others? What doctors have you seen? Do you have any issues with intestinal problems, behavior, autism?”
She could not type fast enough.
What struck me in reading about the families whose children have these rare genetic disorders is that the big, the ultimate, questions about their children’s lives—will she or he speak? ever learn their color and letters? stop head-banging? what will their adulthood be like?—are the ones that are constantly woven throughout my daily thoughts as Charlie pauses to get both of his eyes focused on a new face, or repeats a word over and over again to get the articulation right. (”Airpane, airpwane, airpane, airpane, airplane, airpane.”) I have been so grateful to come into contact with parents of teenage and adult autistic children and, too, to meet older autistic children and autistic adults themselves. I feel very fortunate that Charlie has had a diagnosis that is getting so much attention, and that there are teachers who know how to teach him, and professors and others who understand what methods work best. I appreciate the cautious optimism of Simon Baron-Cohen, who at the start of 2007 noted that ” ‘I remain optimistic that for a good proportion of them [people with autism], it has never been a better time to have autism.’”
My son is autistic. He is disabled—cognitively disabled, with minimal language and abilities to communicate and express himself. Like many of the children with rare genetic disorders described in today’s New York Times, the pathway of his life will require the help and constant support of many others, and the end of that path is highly uncertain. But even though there are many different ways, genetic and otherwise, that have placed us on this path, it seems to me that parents of disabled children share more than a few concerns, and I’m hopeful of learning more.
I have said this before but I do wish more children with autism could be genetically tested so that discoveries may be made in this area. Our daughter was recently diagnosed with an extra chromosome as well and I understand the confusion. We thought it would bring us a new feeling of relief of having an answer. Actually, it caused more confusion since most children with her disorder die before they are born or they die shortly after birth. She is the only one we have found with this specific disorder. Needless to say when she has her days where she appears so sick, has ongoing seizures and just does not feel well….we worry. We also joined a group that searched all over the world for us (Unique) and found no matches of other people with her exact duplication. Even when children have the exact same duplication or deletion the child’s skills and struggles can be totally different. We were also told she meets autism criteria and is considered autistic as well. I don’t regret having the testing done even though we added to our confusion. It has let us know that there are possibilities for organ abnormalities and other health issues we never knew to watch out for.
Wth all due respect to those doing genetic testing, there is still an huge enormous gigantic gulf between knowing a genetic sequence and understanding how that will affect the phenotype of the human who has that sequence.
For example, it is very well known that the gene for the Cu,Zn,SOD is mutated in about 10% of ALS cases and that this causes ALS. Over 100 different mutations in SOD are known to cause ALS, it is dominant, due to a “gain in function” (that is, it is not due to the loss of SOD activity). The mutations are all over the molecule, with seemingly no rhyme or reason behind why each of them causes ALS.
There is no understanding at all of how these very minor mutations (single amino acid substitutions) cause ALS. ALS is trivially simple compared to behavioral disorders such as autism.
It is well known that autism is much more complicated, that it isn’t caused by a single gene, or even by a small number of genes. Identical twins can be discordent for autism.
I am all for encouraging research, but we should not mislead ourselves into thinking that research into autism genetics will lead to any near term treatments (by near term I mean less than 5 years).
We should do for children with autism what helps them now, and for the most part that is the same thing that helps all children, provide a loving low-stress environment where they can grow to achieve their maximum potential.
There is a gigantic amount that we will never know about what causes each big and little quirk and difference in every individual. All we can do is the best that we can based on what we know now. I understand about wanting to be the best parent one can be, and worrying that it isn’t good enough. All good parents worry about that all the time. It is part of being a good parent, always trying to be a better parent.
Interesting piece. Marla’s experience is what I was describing in an earlier comment about genes and environment: having or missing the allele/gene is just the beginning of the story. I know a child who has Williams, and these children are “supposed” to have great trouble doing puzzles or other spatially oriented tasks. He loves puzzles and is good at them. We can’t say it’s because of a different combination of genes, etc…we know exactly what he’s missing from Chr 7.
I wonder how much we’ll continue to find out about kids we’ve described as having autism who turn out to have some very rare single-gene/chromosome mutation that results in similar traits. May be yet another reason it looks like a spectrum…
Our son has Asperger’s (or high-functioning autism, depending on who you are; I actually tend to think of it as the latter) and his prognosis differs from that of Charlie. He’s in a different place on the spectrum. His “symptoms” have improved significantly over the past two years, although it seems to me now that new ones are emerging and some old ones make a comeback in cycles, perhaps triggered by something we cannot detect. I don’t know what his future holds…he still has obvious deficits in some aspects of “self care” and social interaction is a confusing minefield for him. We have these things in common with the family of the child with Williams, and he and our son share many traits, even though their “disorders” differ–or at least the etiologies appear to. I relate completely with your observation about the commonalities among families like these.
And for a child like Charlie, I think that things look more positive today than they would have, say, 20 years ago. As those just ahead of him lay the groundwork for an infrastructure for adults with autism, he may have avenues open to him that were unknown even a decade ago. I often think how mystified we would still be about our own son were people not more aware of these things today. Baron-Cohen had it right, I think.
Amigo is one of 3000 in the U.S. with his blindness, a genetic condition. Our duahgter’s children could have this condition — if her husband is also a carrier. And as of now, there is no test for carrying the trait.
Hey, my son has a 7q deletion–not the same as the one in the NYT story, but then every random deletion is kinda unique (thus the name of the British organization for families of people with rare chromosome disorders). Daedalus2u is right, it doesn’t really answer too many questions to know a kid’s karyotype–it’s an answer, but it’s never THE answer. It helps, some, with getting services, because it’s something definite, it’s a blood test with results. It helps some families make decisions about whether to have more biological kids. But beyond all that… it’s just a string of numbers.
Even two kids with overlapping deletions will be completely different in most of their specifics. Just like kids with Down syndrome are all different; just like kids with a typical set of chromosomes are all different.
Just got home to New Jersey after a day on the plane (and a snowy stop in Chicago): It’s becoming too easy to fly with Charlie. Yes, I never, never thought I would say that: I’m not so sure about what he knows about there being 3000 miles between CA and NJ or how high up the plane flies, but he certainly understands about what happens in airports and is very willing to stay in his seat. I had never thought that he would be able to do this and there are certainly a lot more possibilities for him.
I guess I tend to speak out–”soapvox”—about how kids like Charlie, disable kids, can really surprise a parent, beyond the baleful pronouncements that one tends to receive at the time of diagnosis. Charlie is an example of how, while there has been a tremendous re-ascertaining of our expectations, a child can keep on surprising beyond what one might ever have thought. Neither a diagnosis nor a “genetic aberration” ought to be taken as an all-determining predictor or pronouncement. Charlie just keeps on surprising me—as I try to, in daedalu2’s words,
“provide a loving low-stress environment where they can grow to achieve their maximum potential.”
My son, Jackson, was featured in the NY Times article. I have found the various comments made concerning the article interesting. Each parent of a child with special needs has unique perspective.
I did want to clarify one point. While my husband and I rejoiced in finally receiving a diagnosis, by no means did this end our journey. For us it was the end of a 7 year search to find a name for our daily struggles and frustrations. As stated in another comment, this diagnosis will help us to more effectively plan for the future as well as ease some struggles with therapy services and insurance coverage. We still work each day with our son to help him achieve his greatest potential. Our journey hasn’t ended; it is just more clearly defined. In our case knowledge has been power….. the power to more effectively help our son. CGH testing gave us the knowledge we needed.
It’s really great to hear from you and I was very interested to read about Jackson’s story. It’s a lifelong journey…… many best wishes in the New Year.
Genetic testing would at least give some idea of commonalities and distinctions. Eleanor was tested for fragile X, Rett’s and other syndromes and metabolic disorders, but as was noted by the clinicians, a test does not as yet exist for autism or for her particular pinpoint on the spectrum.
For children who have 2 or more children with autism, PDD or Asperger’s syndrome:
AGRE database
Autism Genetic Resource Exchange
The Autism Genetic Resource Exchange (AGRE) is a repository (gene bank) of genetic and clinical information that is made available to autism researchers worldwide.
http://www.autismspeaks.org/science/programs/agre/agre_participation.php
My 5 year old grandson was diagnosed with Asperger’s Syndrome in the past few months, and now they have found that he is “missing DNA”. Does anyone know what this means for him?
I think that what is being referred to is recently published research about “mutations” of DNA that can take the form of deletions or duplications, as noted here.
I was reading your posts and just wanted to add that because of this new testing my son was diagnosed with 17q21.31 microdeletion syndrome. When we got the diagnosis I was mixed with emotions; releaved to know that I wasn’t crazy my motherly instict was right…there is something UNIQUE about my child. For those of you that have posted and have joined UNIQUE I wanted to make sure that you knew that another GREAT rare chromo support group is CDO (chromosome deletion outreach) and it is USA based. It is wonderful and very active! I also had a question though…Has anyone ever started there own support group here? I have not found a support group for chromosome 17 yet other than parents of Smith Magenis Syndrome which is Chromosome 17 related. So I have started one but have no clue where to go from here. If you can help me please let me know.
@Jacqueline, thanks so much for sharing about your son—-is it a Yahoo groups or other group you’ve started? If you note the site, I can post it here. Motherly instinct is something…..