Home > Science > The Phelan-McDermid Syndrome Foundation

The Phelan-McDermid Syndrome Foundation

Guest Blogger Geraldine Bliss is the Chair of the Research Support Committee for the Phelan-McDermid Syndrome Foundation.

Six years ago, my son, Charles, was diagnosed with Phelan-McDermid Syndrome (PMS), a rare genetic condition caused by damage to chromosome 22 (22q13).  Charles has a chromosome break in the middle of the SHANK3 gene, which codes for the crucial post-synaptic protein, Shank3, mutations of which cause autism.  Charles has a rather small deletion by PMS standards, and he was one of the first patients to be diagnosed with PMS through chromosomal microarray.

Once we learned the diagnosis, our family quickly connected with the Phelan-McDermid Syndrome Foundation (PMSF), where we met, both on-line and in person, other families facing the same challenges.  Just as in the larger autism community, some individuals with PMS were “just like Charles,” while others were very different.  The foundation members were quick to embrace us and make us feel like extended family.  Through PMSF’s biennial conference, regional get-togethers, newsletters, family discussion group, and social networking, our 600+ families are able to stay connected and support each other.

PMSF has grown quickly, but our membership numbers reflect only the very tip of the PMS iceberg.  In the U.S. alone, we estimate there are about 8,000 children with PMS.  Many of these children have never been tested with a chromosomal microarray (the most common test for PMS), either because their doctors have not referred them or because the cost is not covered by their health plans.

Charles is now 12 years old.  Just before his 9th birthday, he started having seizures.  As his seizures spiraled out of control, and we began to exhaust one treatment option after another, I promised Charles to do whatever I could to help him get better.  I became the chair of the PMSF’s Research Support Committee.  Our family crisis, and my new role in the Foundation, occurred at a critical juncture in autism research.  There has been growing scientific interest in SHANK3, a gene on chromosome 22 along with several other autism-related genes, which portend a new era of understanding and medical treatment.

While only about 1% of people with autism spectrum disorders (ASD) have SHANK3 mutations, Shank3 research has broad implications for many people with ASD.  It plays an important and central role in synaptic structure, learning, and memory in autism.  It interacts with many other proteins critical to neurological functioning, and some of these proteins are already implicated in other genetic forms of autism.  A number of researchers have developed mouse knockout models that turn off different parts of the Shank3 protein.  These models have led to behavioral, chemical and physiological assays to study the underlying molecular problems in ASD and to rapidly test candidate drugs for future clinical studies.  Unlocking the mystery of Shank3 will open the door to understanding its partner proteins, providing a research path towards effective drug treatments for many ASDs.

While Shank3 research is very promising, laboratory science by itself will not lead to effective treatments. In January 2010, the PMSF’s Research Support Committee met to develop its first strategic plan for science.  As a result, we prioritized several initiatives aimed at promoting all of the steps needed to ensure that research will lead to clinical gains.  One of the most exciting initiatives is the Phelan-McDermid Syndrome International Registry.   The Registry will collect and catalog information about the developmental, behavioral, and health profiles of individuals with PMS.  The Registry will better characterize PMS, inform clinical care guidelines, and facilitate the discovery and development of therapeutics for PMS.

Our Foundation is also organizing the First International Phelan-McDermid Syndrome Symposium, which will be held on March 3 and 4, 2011.  Our co-investigator is Joseph Buxbaum, Ph.D., Mt. Sinai School of Medicine.  Our goal is to bring together our stakeholders to develop a plan to maximize scientific resources through coordinated efforts and to find the fastest pathways from bench to bedside.  The discussions from the symposium will inform PMSF’s funding decisions as we begin to award grants and fellowships.

Charles’ seizures continue to be poorly controlled.  He has social, behavioral, and communication challenges that affect every aspect of his life.  After all these years, you might think I would have come to terms with all of this, but every day I feel grief.  Sometimes I wonder how much more fear and heartache I can take, but Charles inevitably straightens me out!  Charles has retained a joy that seems incompatible with the suffering he has endured.  Every day his smile and great big dimples tell me he wants to live life and live it joyfully.  How could I not pledge myself to accelerating translational PMS research?  Now that I am involved, I truly appreciate the role that patient advocates can have in both supporting research and helping to steer its course.

We are now at the beginning of a very exciting time for research related to disorders like PMS and other genetic causes of autism.  Advances in science, including the mapping of the human genome, new research tools, and new high-throughput drug discovery paradigms, are reshaping expectations about understanding and treating genetic conditions.  Our group’s goal is not just finding medications to treat some of the manifestations of PMS, but having therapeutics that will target the underlying molecular causes.  Just a few years ago, I had little reason to expect significant help from medical science, but promising new scientific work on Shank3 is inspiring hope that perhaps we will one day have a cure for PMS and related ASDs.

To learn more about the Phelan-McDermid Syndrome Foundation, please visit:  http://www.pmsf.org

  1. sandra motonaga
    January 11, 2011 at 12:47 pm

    Thank you sooooo much for sharing your story…my son, Gabriel, was diagnosed with Phelan McDermid Syndrome 2 years ago. He also has Autism and a rare form of hydrocephalus, a lifethreatening allergy to peanut trace products, eosonphilic esophagitis, scoliosis…to name a few amongst a total of 9 different diagnoses. It is a blessing to have come across your story on FB. Did you know that some forms of the seizures are often mistaken as seizures but in reality are related to eosonphilic esophagitis? We were fortunate to meet with the wonderful Dr. Margaret Bauman. She is affiliated with the Autism Center out of Harvard Medical School. Her research has found there is a common health issue amongst autistic children – the problems with their esophagus – the acid that comes up and irritates the individual’s esophagus causes immense dicomfort, vomiting and such – sometimes the behaviors may be mistaken for a seizure. Has your son had his esophagus scoped? It sounds invasive, but my son was under general anesthesia and everything went smoothly. If it were not for this procedure, we would neve have know about this diagnosis. We are treating it and it has reduced many physical reactions, we once assumed were only seizures. I am not saying your son does not have seizures, but I wnated to be able to share anything I can. sometimes it is lonely not having a circle of immediate support from people who are really not in “our shoes”. God Bless you. – Sandee

  2. Tony Castrilli
    January 11, 2011 at 1:02 pm

    Thank you for this important update, and outlining the significance of the March meeting. The research is good news, and I look forward to supporting the work of the Phelan-McDermott Foundation. My four year old daughter Sophie was diagnosed with PMS in 2009. Like you, my family continues to find joy in the small victories while coping with an uncertainly future and a the profound sadness of Sophie’s illness. Please keep up the good work. Tony Castrilli

  3. Mindy
    January 11, 2011 at 1:45 pm

    Charlie is SUCH a handsome young man! I have a 26 yr old son with Asperger’s. I am always interested in strides made toward improving the lives of all people with autism and their families. While I am not exactly in your shoes, my son had petit mal seizures up until the age of 15. We were told that it would be most unlikely that he would ever graduate from high school. I am happy to report that through love, nutrturing, blood, sweat and tears, he is a happy, healthy, funny young man, living on his own in another state-making his way on his own terms, just as we had always prayed that he would be able to do someday-just like anyone his age would want! God bless all of you!

  4. RAJ
    January 11, 2011 at 3:07 pm

    The NIH has a reference guide for genetic syndromes and a detailed description of each genetic syndrome. Here is the NIH’s page on Phelan McDermid Syndrome:

    http://ghr.nlm.nih.gov/condition/22q133-deletion-syndrome

    What have the genetic counselors told you about the recurrance risk since most cases are not inherited.

    • Andy Mitz
      January 12, 2011 at 11:18 am

      I know you asked Geraldine about recurrance risk. May I answer? So far, the only risk of recurrance is if the child has inherited something from the biological parents. If at least one parent has a balanced translocation that involves the terminal end of chromosome 22, then recurrence is likely (about 1 in 4). This condition is easily identified in the parents. Test results in the child will often point to this possibility. There are some other rare, but possible inherited causes for PMS and testing for these causes will probably await lower-cost gene sequencing.

      Andy Mitz
      Father of a 25 year old son with Phelan-McDermid Syndrome

  5. Hilda
    January 11, 2011 at 6:32 pm

    Awesome Geraldine. We, by the way, talked with our pediatrician in December and we are going to pursue the genetic testing. I hope you don’t mind that I’m sharing this link to my Twitter followers. You did an outstanding job.

  6. Teri D
    January 11, 2011 at 7:38 pm

    I read your article with great empathy and respect for your strong sense of advocacy, urgency and hope. I too have a family member with PMS and it has been a journey filled with many emotions. The PMS foundation is an exceptional group of individuals and a huge source of information, support and love…

  7. January 12, 2011 at 1:33 am

    Hi,

    I run a project at the Autism Research Institute looking at the relationship between autism and high levels of oxalate in the body. Autism is comorbid with a lot of genetic conditions and so far, we are finding that reducing oxalate in the diet is helping many children and/or adults with these conditions that have a high risk of autism or autistic features, such as Rett syndrome, myotonic dystrophy, multiple hereditary exostoses, Angelman syndrome, celiac disease, and more. We also have seen this diet resolve seizures occasionally.

    Oxalate is toxic especially to the mitochondrion, and it is also an antinutrient that is higher in some plant foods than others. Its effects are dose-related, but it slowly builds up in the body, which may account for some of its consequences taking years to present.

    What can help in analyzing the relevance of this issue in Phelan-McDermid Syndrome is a lab test offered through Great Plains Laboratory for organic acids that also tests oxalate. I can help with the interpretation of this test since I have already analyzed almost 300 of these tests for those with autism.

    My suspicions are that a lot of genetic diseases with comorbidity to autism may have a leaky gut for very different reasons, or may have problems with pyridoxine, which also leads to high oxalate. If there is a “leaky gut”, then the usual absorption of 1-2% of oxalate that is in the diet can increase as high as 505.

    In our project, we just lower the percent of oxalate in the diet by selecting fruits and vegetables that are lower in oxalate. The changes have been remarkable and now we have six years of experience monitoring this diet in autism and with individuals with various conditions who are part of a listserve our project runs that now has more than 3400 people on it.

    I’d love to talk to someone in your foundation about this if you can contact me.

    Best wishes,

    Susan Owens
    Head of the Autism Oxalate Project at the Autism Research Institute
    The project office is in the Dallas, TX area.

    • Andy Mitz
      January 12, 2011 at 11:12 am

      Susan,

      I have no idea if oxalate, or sugar, or carbohydrates, or any of the 500 other food items, diets or drugs that have been suggested as a treatment for autism will have any benefit for someone with Phelan-McDermid Syndrome. Rather than have every child try every diet or undergo every metabolic test, it will be much more productive to look at the science and do better science. The primary defect in the Syndrome is loss of Shank3. With a few minutes of research, you will see that Shank3 is common in epithelial cells. Thus, there is strong reason to believe that the GI tract is affected by Shank3 loss. With a little more research, you might find a connection between oxalate and Shank3-related epithelial transport. After doing your homework, I highly recommend you contact the Phelan-McDermid Syndrome Foundation and make your recommendation. As Geraldine points out, the Foundation is building a registry for researchers to investigate potentially valuable treatments. It is a family partnership with science and hopefully the future of finding effective therapies.

      Andy Mitz
      Father of a 25 year old son with PMS

    • Geraldine Bliss
      January 23, 2011 at 11:03 am

      I’m sorry for the delay in replying.

      One of the most frustrating issues for any parent raising a child with ASD is the lack of evidence-based clinical care guidelines. What works for one person with ASD does not always work for the next, which underscores the heterogeneity of ASDs and their underlying causes. Phelan-McDermid Syndrome and other genetic forms of ASD provide scientists with very specific starting points for understanding the underlying molecular problems in ASD. Through the knowledge that is being gained about the Shank complex, investigators are beginning to understand the pathophysiology of Phelan-McDermid Syndrome, which will inform treatment options.

      You mention you have suspicions about leaky gut in genetic conditions. In PMS, specifically, there is no scientific evidence to support that theory. In fact, there has been very little published at all about the role of Shank3 in the GI tract. There were a couple of recent papers I was excited to read, because they provide a bit of a theoretical basis for future GI-related studies in Phelan-McDermid Syndrome. I’ve provided the links below.

      Susan, if this is a research area you are interested in pursuing, I would encourage you to attend our symposium. It will be a terrific opportunity to talk with scientists (mainly neuroscientists) who already have model systems for studying Phelan-McDermid Syndrome and may be willing to collaborate with GI researchers.

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693461/?tool=pmcentrez

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172453/?tool=pmcentrez

  8. Michelle Dyson
    January 12, 2011 at 12:46 pm

    Thank you so much for posting this and sharing your experience. Despite my years and years of Googling “hypotonia and autistic spectrum disorder,” I’d never heard of Phelan-McDermid until your blog came through my Autism Speaks Facebook newsfeed yesterday afternoon.

    My husband and I are blown away by how many characteristics our son shares with this population — so much more so than with the couple of dozen ASD kids I know through my local community. So we now have an appointment with a geneticist through the Denver Children’s Hospital — but not until April! Are there any experts you would recommend us speak with? Maybe we could get in earlier than April or have a blood draw sent to a lab for this specific test.

    Thanks again for posting this. Knowing more about the cause of my son’s ASD would mean a lot to us.

    • January 15, 2011 at 8:11 am

      As Geraldine mentioned, chromosomal microarray (CMA) is a common test for Phelan-McDermid Syndrome. CMA is also known as array comparative genomic hybridization or aCGH. Most genetic departments and sites are running this test, including the University of Colorado Genetics Laboratory. Please take a look at GeneTests for additional sites that may run aCGH:

      http://www.ncbi.nlm.nih.gov/sites/GeneTests/clinic/location/?db=genetests&state=CO

      Alex Kolevzon, MD, the Medical Director of the Seaver Autism Center, can give you more information. He can be reached through theseavercenter@mssm.edu

      • Michelle Dyson
        January 15, 2011 at 11:44 am

        Joseph, thank you — but now I am in a panic. We are taking my son to our local hospital lab to get a blood draw this morning for a FISH test — which I read on the 22q13.org website was the way it was Dx’d. Should we wait and ask for this CMA test?

    • January 16, 2011 at 10:24 am

      I, too, had googled everything and everywhere possible and never came across PMS. My daughter was diagnosed with PMS this summer after 7 years of frustration.

      What I would like to add is that it was only because of medical advancements with regards to the coverage of the microarray that we were able to figure out the diagnosis. She had a microarray at age 2 and nothing was found. 5 years later, at age 7, she tested positive for a 22q13.33 deletion.

      • Michelle Dyson
        January 16, 2011 at 12:22 pm

        Thank you for chiming in, Cynthia. With some quick texting and a last-minute call to our pediatrician on a Saturday, I was able to get both the FISH test and CMA test ordered and blood draws completed. We still have an appointment scheduled with the geneticist in April, regardless of the outcome, but I do hope we have some answers sooner than later.

    • Geraldine Bliss
      January 23, 2011 at 12:21 pm

      Hi Michelle. I’m glad that you were able to get the blood draw for the CMA arranged so quickly!

      I think it’s a good idea to start with the geneticist in your area. They will usually make referrals to the other specialists your child might need to see, based on the clinical evaluation in the genetics clinic and CMA results.

      If your child does indeed have PMS, please register with our foundation: http://www.pmsf.org. We can help you connect with other PMS families in your area.

      I hope the CMA is able to provide you with some answers about the cause of your son’s ASD.

      • January 27, 2011 at 7:19 am

        Michelle, sorry not to reply sooner – I did not see your post.

        As Geraldine said, it is great that you could arrange the CMA, and by texting no less!

        No test is perfect and both together would be extremely reliable. FISH readily detects larger deletions but there are small deletions that are better tested with CMA.

        Wishing you all the best,
        Joseph

  9. Katie Wright
    January 12, 2011 at 1:52 pm

    What a beautiful boy. He is adorable.
    I hope you are able to find something to control his seizures. I know that can be devastating.
    I wish you nothing but the best of luck in solving PMS. I very much wish your son and all PMS kids have the all help they need.

    I however, respectfully, see PMS and autism as very different diseases, with common behavioral challenges yet with very different causative factors. PMS has not increased 600% in the past 12 yrs, and unless I am wrong it is not primarily environmentally triggered. Children do not suddenly descend into PMS. That said I hope Buxbaum and his team are able to do their absolute best in devising treatments of PMS. Good luck with your conference.

    • Michelle Dyson
      January 12, 2011 at 3:19 pm

      Kate, respectfully:

      1. Since the syndrome was identified 20 years ago, 450 children have been diagnosed with it. So, I guess that’s a 450% increase?

      2. I don’t think it’s yet been established how the chromosome is deleted in PMS; it may very well be an environmental trigger.

      3. Not every child with an ASD suddenly descends into it.

      There are already several syndromes that are placed within the ASD umbrella (Rhett’s, Fragile X) where we know the genetic makeup. I’m hopeful we will eventually be able to identify every autism this way.

    • Andy Mitz
      January 12, 2011 at 9:41 pm

      Thank you for your kind words about the families with PMS.

      The Autism diagnosis is defined in DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition). The definition says nothing about what causes Autism, how prevalent it is, or how many new cases are seen each year. It is a developmental disorder. It is defined by just a few critical behaviors, like social interactions, communications, and repetitive behaviors. If you would like to change the definition of Autism, there is a committee of specialists are working on DSM-V right now. You can register with the web site (http://www.dsm5.org/) and submit your suggestions. Until the year 2000, children and adults with PMS simply had Autism. Now that scientists have found a causal gene, did the Autism just go away? Of course, not. Individuals with PMS have Autism as much as anyone else diagnosed with Autism. There are about 40 known genetic defects that have a high likelihood of producing Autism. PMS is only one of them.

      As Geraldine suggested, the fact that there are different causes of Autism may be of immense benefit to us all. Seizures are about as common in people with Autism caused by the missing Shank3 gene as they are for all people with Autism. Wouldn’t it be wonderful if, while studying this rare cause of Autism, scientists learn the critical link between Autism and seizures? I have met Geraldine’s son and he is every bit the sweetheart you see in the picture. But, my heart goes out to every family dealing with Autism and seizures. I see great hope for everyone affected now that there is a chance to really understand a few special cases of Autism.

      Andy Mitz
      Father of a 25 year old son with PMS

  10. richard fauth
    January 12, 2011 at 8:24 pm

    Hi to all who already know me (Geraline, Andy, Dr. Buxbaum other pms folks) and a very glad to be able to speak to those of you who do not. I am the father of a seven year old boy with Autism who has two variants within the shank 3 gene and a variant within the cntap2 gene. Research on my son conducted thus far, currently indicates that the more significant variant within the shank 3 gene is not likely the cause of his Autism. But stay tuned- 8 months ago this same variant was believed to be absolutely the cause of his autism. My point? You cannot do it it until you do it. Valid research is difficult and requires a lot of discipline- Just because some researcher believes something is true doesn’t make it so-the research still has to be conducted and even then even more will have to be done to get to the bottom of what is going on with our children.

    So I am sorry,katie, that you feel the need to dissuade others-i’ve read other negative comments concerning gene research from a katie wright in the past and felt the need then and now to challenge your statements. First and foremost your statement that PMS kids have not had a 600% increase in 12 years is misinformation since PMS was officially discovered in 1998. Your statement that Autism is a differant disease than PMS is also backwards. Autism is likely a bunch of diseases including PMS.

    We see again the dangers of “buying in” to media driven quackery in the recent press revelations that Dr. Wakefield had applied for patents and had a financial stake in the outcome of his now known to be fraudulent research.

    So stop it. Those behind genetic research do not discount that environmental factors play a part-only that well over a decade of blaming thimerisol produced nothing usefull for our kids and doing the same for the thousands of chemicals out there will take thousands of decades.

    We need an “army of researchers” starting with the valid research that starts with genetics-and moves into all the things in which that research leads to. We aren’t going to get there if the energy and funding is wasted with charlatens backed by “authors” who think a charlaten is a nice guys- and therefore couldn’t possibly be a crook. How much did the “Author” make exploiting the parents of kids with Autism?

    Kudos to the researchers involved with Fragile x, Retts syndrome, PMS, angelman syndrome, timothy syndrome and all the other genetically implicated developmental disorders- you have done alot with very little-thanks.

  11. Marie Demachy Fauth
    January 12, 2011 at 9:26 pm

    I have a 7 years old son with autism and an abnormal EEG. My son had genetic tests; results : 2 variants on Shank 3 and one on CNTNAP2 (2 autism suspect genes related to synapse development) but no deletion. Thank you Katie for your comment but Autism is not a disease, Autism is a range of symptoms expressed from a biological disorder (like fever for the flu) and seizures are part of the symptoms too. When you explore a syndrome like PMS or Rett for example, you will find that autism expresses differently but also with common features, deletions on a chromosome can stop several genes at the same time so you can have different forms of physical and autistic features. These features are the proof that the symptoms of autism are linked to genetic. Since the creation of the Univers, genetic has evolved with environment, environment is probably linked to the field of autism (and everything else). The world of “autism” is lucky to have the Phelan McDermid syndrome foundation. It’s a strong and active foundation that has a goal: helping to understand the mechanisms of autism (and seizures)in their children. Thank you Geraldine and Autism Speaks for this article.

  12. Katie Wright
    January 13, 2011 at 11:22 am

    I don’t disagree with any of you!
    Parents know your children better than anyone else.

    I stand corrected about the rise of PMS, I apologize. I think we can respectfully agree to disagree about the research. These disorders all deserve attention and research but they do comprise a tiny % of overall ASD.
    I think we can all agree that too many children are suffering everyday. Mine has autism the disease- terrible IBD and severe auto immune dysfunction. Maybe your children have seizures and other co-morbid conditions. I should have states my point that we all need more here and now help and clinical research, or at least my son does.

    • Andy Mitz
      January 13, 2011 at 8:56 pm

      Katie,

      You are so right. We need working treatments now. There are too many families suffering.

      We can agree to disagree about the research. In 1971 President Nixon declared war on cancer. He boosted science funding. The scientists put all their efforts into understanding normal, healthy cells, genetics, and things there seemed to Richard Nixon as nothing to do with cancer. He was actually quite angry with the NIH. But, this is how scientists work. Now, 40-years later, testicular cancer (1 in 250 men) is cured 95% of the time, breast cancer can be cured 70 to 85% of the time, another common cancer, prostate cancer, has a 90% survival with early detection. Over 70% of childhood cancer is curable. These are amazing results. Did the scientist waste their time getting them? I would like to think not. Because, not only has cancer research helped many, many people, but the early research has laid the foundation for more successes yet to come. Do people still sufferer from cancer? Yes, 12 million people will die this year world-wide. That is a lot of suffering. There is a lot more to do, but the tools and understanding gained in the last 40 years puts cancer cures light years ahead of Autism.

      Cracking the code of cancer was all about genetics and molecular biology. These are the best tools in the current scientific toolbox. The rare forms of genetically-based autism (which as a group add up to a significant percentage of all Autism), are the ones that can be studied with the best tools of science. I agree with the Autism researchers who take this approach. Right now the goal is to understand the basics of Autism. The hope and prayer is, if you can cure one form of Autism, the rest will follow. As we know from cancer, it is never that simple. But, genetic-caused Autism is the big hope right now. The choice makes sense.

      My son is 25 and, given the toll Phelan-McDermid Syndrome has already taken on his development, he would never benefit from a treatment like a young child might. My push for research is aimed more for all the other families who are dealing with, or will be dealing with, Autism and Autistic Spectrum Disorders. We need to support research and we need to support each other.

      The Phelan-McDermid Syndrome Foundation is pushing researchers to keep their eye on medical treatments, not just science. Geraldine is at the forefront as the Chair of the Research Support Committee. She never let’s the scientists forget that, to us, this is not just research, it is hope.

      Andy

  13. Mary Pierson
    January 14, 2011 at 10:42 am

    This is a fascinating discussion, and I will share it, individually, with many others who have a family member or a friend or a student, or have some other special connection and reason for their interest. Thank you, all who have taken time to post. Mary

  14. January 15, 2011 at 7:47 am

    Thank you Geraldine for you very moving piece. I also very much appreciate the heartfelt responses from all the others here. I was so moved that I have decided to give my perspective, both as a scientist and as someone who has become more involved with the Phelan-McDermid Syndrome community.

    This is an amazing time for translational research in neurodevelopmental disorders (which include Phelan-McDermid Syndrome and autism, as well as other disorders). Some of the roots of the recent advances have been alluded to in the discussions above. In the past, these conditions were diagnosed behaviorally. Autism, for example, is an entirely behavioral diagnosis. A diagnosis of autism says nothing about the cause of autism. Through advanced molecular and genetic work, we are beginning to introduce what are being called etiological diagnosis. What that means is that the cause of a condition is known. For example, Geraldine notes that Shank3 mutations are a critical part of the etiology of individuals diagnosed with Phelan-McDermid Syndrome and, in some cases, of individuals diagnosed with autism.

    By understanding the molecular changes that underlie a condition, scientists are now able to generate model systems to study the effects of the molecular changes with the hope of developing new treatments. In Fragile X syndrome, tuberous sclerosis, and Rett syndrome (three other neurodevelopmental disorders) there are clinical trials going on that have resulted from these kinds of studies. There is already some suggestion of positive effects in the clinical trials for Fragile X syndrome. It is our hope and expectation that similar breakthroughs are going to be happening in Phelan-McDermid Syndrome.

    I and the people who work with me feel privileged to be working with the autism and the the Phelan-McDermid Syndrome communities. We also deeply appreciate the input and the support we have received from people such as yourselves and from foundations, including Autism Speaks, the Seaver Foundation, and the Phelan-McDermid Syndrome Foundation.

    Best wishes for a transformative 2011,
    Joseph

    PS We are committed to doing a better job at keeping our website about Shank3 (www.shank3gene.org) more up-to-date and hired someone to help with this!

  15. Mequet Mcdonald
    January 15, 2011 at 12:48 pm

    Thank you for the blog. My nephew was diagnosed with PMS about 10 months ago. He is going to be in the first group of clinical trials at Mt Siani medical center for Human Insulin Growth Factor. We are all very excited and hopeful.

    • January 17, 2011 at 11:02 am

      This has been a fascinating exchange and it is inspiring to see how much interest there is in participating in research. At the Seaver Autism Center, we are extremely committed to studying neurodevelopmental disorders on the autism spectrum and their many complex causes and have been privileged to meet many families touched by Phelan-McDermid Syndrome over the past six months. Dr. Buxbaum has made significant progress using a model system of SHANK3 deficient mice and, in parallel, we are in the midst of genetically and clinically evaluating affected individuals and their families.

      In thinking about the design of a future clinical trial, it is critical that we learn more about the diverse ways in which Phelan-McDermid Syndrome presents and which signs and symptoms could be targeted for improvement. At the same time, Dr. Buxbaum is exploring the utility of several pharmacological compounds in the model system as potential treatments, including IGF1. We do hope to be starting clinical trials in the near future, but several steps need to occur first: 1) complete the pre-clinical trials to identify lead compounds; 2) obtain permission from the FDA to use the compound for research; and, 3) secure funding. I have been asked a lot about the anticipated timeline, and once we know exactly which compound/s we intend to take to clinical trial, the timeline will be clearer.

  16. Jane
    January 16, 2011 at 11:05 pm

    I understand that 1% of people with autism have PMS. On the other hand, what per cent of people with PMS have autism? And is it known what per cent fulfill one, two or three of the criteria for diagnosis of autism? Thanks very much for any answers or references.

    • Andy Mitz
      January 17, 2011 at 1:02 pm

      You ask an excellent question. The answer is difficult. It is difficult to get a good sample with a rare disease and with a consistant standard of diagnosis. The school psychologist refused to issue a diagnosis of Autism when there was already a PMS diagnosis. The top researchers/clinicians in Autism have told me (directly) that such a refusal ignores the diagnostic criteria. So, the diagnosis must be done by a single, qualified group of professionals who apply the same standards regardless of other diagnoses. The upshot is that many PMS children do and many don’t have an Autism diagnosis. Another problem is that Autism is a developmental disease. A large proportion of the PMS children are too young to see Autism yet. For these reasons, the registry and future research will be very important.

      Here is what is known. The Autism diagnosis is common among older children with PMS. Most probably fit on the ASD spectrum. There are several studies that show a significant percentage of patients diagnosed with PDD-NOS have PMS (except that was not found in one study from China). Perhaps more interestingly, Shank3 is one of the commonly found genes to be different in the Autism population. Here is a great reference to get the exact numbers:

      Betancur C.
      Etiological heterogeneity in autism spectrum disorders: More than 100 genetic and genomic disorders and still counting.

      Brain Research 2010 Nov 30. [Epub ahead of print]

      Andy Mitz

    • Geraldine Bliss
      January 23, 2011 at 11:44 am

      Hi Jane. We don’t know the exact percentage of PMS patients with ASD, for the reasons Andy Mitz explained. Because so many families report autistic behaviors or a formal diagnosis of ASD, we recommend that children with PMS be evaluated for ASD. Click here to view our recommendation: http://22q13.org/j15/index.php?option=com_content&view=article&id=155&Itemid=150

      In order to have a formal diagnosis of autism under DSM-IV, patients must meet all three criteria. My son, for example, has social impairments, communication impairments, and repetitive/stereotyped behaviors. Charles was formally diagnosed with autism through an ADOS evaluation.

  17. Gina Longo-Parkes
    February 28, 2011 at 12:23 pm

    I am so glad that I was able to read through this information here! I was 39 while pregnant with my son Zeke (now 10). I was told by a UCLA genetics doctor that because of my advanced age I should have an amniocentesis. Because a 2nd cousin had died of DiGeorge Syndrome, extra amnio fluid was extracted for a FISH test we to see if there were any any deletions on chromosome 22. According to the pathology report there were NONE. We started to see the signs of severe autism when Zeke was less than two. For years we tried so many different behavior therapies speech, ot, sensory etc. and none have worked. Last year we took him to a local pediatrician who had vast a knowledge of autism and he ordered blood tests for Zeke, and one was indeed the SAME FISH test that I had had in utero with the amniosentesis. Sure enough the pathology report states that there appears to be a small deletion on chromosome 22. We brought Zeke to the same UCLA genetics dr. and when I asked HOW this could have happened she replied that it was just ‘rotten luck’. I love my son to death but I was very local about what I would have done in the event that amniocentesis had evidence of a disability. My son is a happy child although his pediatrician says that Zeke is terribly low-functioning…just in a big body! He will need 24/7 care forever and my husband and I are both heartsick and angry. We are low-income and cannot afford this type of care and are able to just get what the state offers which very little with CA. being a ‘broke’ state.

    Here’s the irony…when Zeke was born I named him ‘Austin’ but the day after changed it to Zeke for fear that “Austin’ sounded too much like “Autism”. My husband was made because he was afraid of kids maybe saying things like Zeke the freak, etc…so now he ends up being autistic anyway!

    • Andy Mitz
      February 28, 2011 at 6:08 pm

      Gina,

      Your experience of frustration, anger and unfairness feel so familiar. Our experiences date back before PMS was identified. Our first son almost died as a newborn because of PMS. He is quite severely affected. We were told by a top specialist that this unknown genetic problem must be very rare and not to worry about a recurrence. On the second pregnancy we did CVS testing just to be more sure, but the CVS did not go well and that fetus died. It probably would have been a “typical” child. Our third pregnancy lead to a second child with PMS (I am a carrier of the more rare inherited form). She died as a newborn.

      We feel lucky that we have found a group home for our son. The irony, of course, is how unlucky you must be to have that sort of good luck.

      I used to get very mad at the mistakes and bad luck. There are so many battles. I know.

      Andy

  18. Julie Barclay
    April 16, 2011 at 6:07 pm

    My son got diagnosed with Phelan McDermid Syndrome 22q13 just recently at the age of seventeen (17) … It doesnt change who he is, it just helps us to understand a little bit more after all these years why his communication and speech is all mixed up and why he has severe Learning Difficulties And low muscle tone …

  19. Cathy
    June 11, 2011 at 9:55 pm

    Our 30 yr old son was recently diagnosed with Phelan McDermid Syndrome – almost a relief after for all these years of not having a diagnosis even with all types of testing and doctor visits. I am stuggling to learn more about this in adults. It seems there is little info available and what is available is targeted more towards younger children. Or the info is heavy in medical terminology.

    Any info is helpful. Thanks

    • Andy Mitz
      June 12, 2011 at 1:13 pm

      Cathy,
      For now, until the research brings more answers, you can share your thoughts with other families in the Phelan McDermid Syndrome Foundation. The two main gathering spots on the Internet are a yahoo group ( http://health.groups.yahoo.com/group/22q13/ ) and the 22Q13 Families group on Facebook. You are right, most of the information is for small children. They are the ones most often diagnosed. But we have Foundation members with sons and daughters up to age 46 (if I recall correctly). At the Region 4 meeting (Mid-Atlantic US), I have met family members of affected adults age 28 and 46, plus my son who is 25. We are all aways happy to share notes. Also, whenever you find the science or medicine discussion gets too technical, contact the Research Support Committee. It is their job to help translate the complex technical talk into something meaningful for the families. You can reach me all three ways and I am happy to share notes about my son. I hope these leads are helpful to you. By the way, if you can, consider entering your son’s information into the PMS Registry. The Registry is the future for improving science and medicine for all of our children.
      Andy Mitz

  20. June 12, 2011 at 1:17 pm

    Cathy…check out 22q13.org and become a member. This is free. Once you do that…get in contact with your regional representative. The site also has links to facebook and yahoo groups. The facebook group is very active and does have a few members who have adults with PMS. You should also fill out the PMS registry when you have time…this is the best way for us to leave more about our kids and how PMS affects them. You’ll see the registry information right on the front page of the website.

    My daughter is 8 and was just diagnosed last year!
    Cynthia

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  22. January 1, 2012 at 2:42 am

    Medical insurance is for more than just paying hospital bills. Family medical insurance can protect your family’s health. Many people call to get private health insurance quotes for policies that they only plan to use in an emergency. They rarely consider that the insurance is also created to help them maintain their health. Medical insurance comes in various flavors. Some are comprehensive and will cover a myriad of services; others are very streamlined and are created to only cover basic services. It is important to determine which type of policy you will need. While it is hard to predict exactly what may befall you or your family, it is always best to try to find a policy that will cover at least most of life’s events, such as maternity care

  23. MERCHE
    January 16, 2012 at 7:45 am

    Mi hija tiene 4 años y medio. Empieza a decir alguna palabra, poca cosa, mama,papa, agua… Como un bebe que empieza a decir cositas. Camino con 30 meses. Su comportamiento no es siempre bueno. cuando se enfada pega a quien tenga a su alrededor, aunque luego da besos y pide perdón. Acude al logopeda y va a la escuela ordinaria. Ella come y duerme bien, y goza de buena salud. No sé cuando daño tiene su cromosoma 22. Es un camino muy dificil. Yo estoy muy afectada. lo siento, pero tengo fé en que mejorará. feliz año 2012.

  24. Nathan Bliss
    January 24, 2012 at 9:09 pm

    Charles is a great kid. He is very talented, loving, and lovable. Charles means a lot to all of us and he is always in our hearts. I love Charles very much as his eleven year old brother.

  25. Angy
    February 11, 2012 at 9:26 pm

    What is the prognosis for a person with PMS, that is caught early on? I have a special little girl that I care for on a daily basis. I am very familiar with generalized autism and have multiple years of experience with adults who have this disorder but the specific PMS diagnosis is new to me. She developed the epileptic aspect of PMS in 2009, when she was four. Before she developed the seizures, she was beginning to speak, things like “Momma, Da-da, Potty, Eat,: etc. Now, however, she has backslid to a more infantile stage. She once was able to use the bathroom on the toilet, and now has no ability to do so, we are trying but with no avail. She says very slight terms- “right der” (right there) and has started to say a version of my name “Annie” ..which is actually Angy.
    She is a technological genius, I swear! She knows how to use an i-pad, all sorts of video games, can turn on and re-program the TV! She knows how to sneak onto the internet on her i-pad and order new applications! She knows more than me!
    This disorder is just so rare, her parents and myself feel as if we are feeling around in the dark. We are trying so very hard, but progress is slow and we just worry we are not doing things right. What can we do to help speed things up? I want to reach her now while she is young and has the ability to absorb things more easily. What can we expect her to be able to do in the future? Are there possibilities of her communicating verbally? Using the bathroom on a toilet?
    She is just the biggest sweetheart, I love her so much and want to do everything I possibly can to help her grow and develop into a functioning young lady, whatever that means for her!

    Thank you so much for your help! We need it!

    Angy

    • Andy Mitz
      February 12, 2012 at 11:37 pm

      Angy,
      The Phelan-McDermid Syndrome Foundation is dedicated to supporting families and caregivers struggling with (and celebrating) the challenges of PMS. You can reach the PMS Foundation through their web site and through their Facebook page. Questions like yours are addressed by scores of parents every day on Facebook, so that is a great place to start. One thing I can tell you now is that your story is familiar. As for prognosis, none of the children have grown up to be independent. Also, seizures are common and some families struggle a lot trying to keep seizures under control.

      Please contact the group. You are welcome to email me directly. arm [at] gnode [dot] org.

      Andy

      • Andy Mitz
        February 13, 2012 at 5:44 pm

        Oops. I forgot to leave the contact information for the
        Phelan-McDermid Syndrome Foundation

        Web site:

        http://22q13.org/j15/

        Mail:
        Attn: Sue Lomas, President
        Phelan-McDermid Syndrome Foundation
        P.O. Box 1016
        Venice, Florida 34284

        e-mail
        Sue Lomas President/Executive Director sue@pmsf.org
        The Office Administrative Assistant office@pmsf.org
        Phone 1-941-485-8000
        Fax 1-941-485-8000

  1. January 12, 2011 at 11:19 am
  2. December 16, 2011 at 6:02 am

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