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Rett Syndrome and the DSM V

February 22, 2010

As many parents may already know, the Diagnostic and Statistical Manual of Mental Disorders, known as the DSM, is in the process of reevaluating criteria for the new edition to be published in 2013, the DSM V. There is discussion among members of the Rett community and the Asperger’s community about the decisions to drop both diagnoses from the manual. How this change might impact services, particularly intensive educational intervention for Rett children, is unknown and will probably vary from state to state. People who would like to express their opinions to the DSM committee may do so until April 20, 2010.

RSRT scientific advisory board member and Rett Syndrome researcher Huda Zoghbi , M.D. discusses the DSM reclassification with Monica Coenraads.

Huda Zoghbi will be appearing on the Charlie Rose Show on Tuesday, February 23, 2010. The episode, entitled “The Developing Brain” is part of the “Charlie Rose Brain Series” hosted jointly with Nobel Laureate, Eric Kandel, Ph.D. of Columbia University.

MC: What do you think was the impetus behind removing Rett Syndrome from the DSM?

HZ: My understanding is Rett was originally included in the DSM because it was a disorder with autistic features of an unknown cause. Now that the genetic cause has been identified, the rationale for removing Rett is that it is more its own distinct entity. Another reason pertains to the transient nature of autism features in Rett patients but this is not exactly the case. Rett patients do not have language skills and continue to manifest stereotyped behaviors for decades. Although some might acquire some social interaction skills through eye-pointing this is not true for all cases.

MC: Yet, if knowing the genetic cause of a disorder is the rationale for exclusion, in time, as more genetic underpinnings of disease are identified there will be fewer and fewer left for categorization by the DSM.

HZ: Correct. That is why I actually do not agree with this approach. I think the approach should be to see what clinically fulfills criteria for autism. I would be in favor of a more precise categorization and dividing DSM V into two types: DSM V A and B. One would be used for syndromic autism and one would be non-syndromic autism. There would be genetic etiologies for both syndromic and non-syndromic. Currently most of the known genetic causes are for syndromic autism but in time, as we do more sophisticated sequencing and we study patients with simplex autism (one case in a family, with no features other than classic autism) we will find etiologies for non-syndromic as well. In my view this would be a much more useful distinction. Bottom-line: having a known genetic cause should not eliminate a disorder from DSM V.

MC: The decision to remove disorders identified with a genetic cause seems very black and white to me. While knowing the root cause of a disorder is hugely important it often also brings many unanswered questions. Let’s look at Rett Syndrome itself – a certain percentage of girls/women with a clinical diagnosis of Rett do not have an identified mutation. And then we have individuals with MECP2 mutations who do not have Rett Syndrome symptoms. So, using Rett as an example of a genetic disorder, the situation is certainly not black and white.

HZ: Absolutely. In fact, the girls who have MECP2 mutations who fit the clinical criteria for autism and do not have Rett symptoms make a very compelling case against the current draft of DSM V. They represent a troubling scenario for an important patient population – what diagnosis do we give them? Where do they belong? So now with the proposed DSM criteria we have a category of patients that are left unattended to in this manual.

MC: It seems to me that the Rett clinical community, in general, was in favor of removing Rett. Do you have any insight into their reasoning?

HZ: The medical community appropriately focuses on clinical management: what treatments can be delivered to the patient, what code is used in the medical records for billing purposes, etc. These issues have probably driven the support of the clinical community for removal. On the other hand, if you are about solving the puzzle of these brain disorders and understanding the pathogenesis of the autism phenotype in Rett and beyond, then removal doesn’t make much sense to me. If you believe that the DSM manual is a tool to help us better understand brain diseases and to highlight the commonalities and differences between them, then I don’t feel taking out Rett serves the cause of disease-oriented research.

MC: Once DSM V is finalized will we be able to call Rett an autism spectrum disorder or will that be a misnomer?

HZ: I don’t think it will be a misnomer because clinically Rett is an autism spectrum disorder. Just because it’s taken out of a manual does not change the phenotype of the disorder. Imagine, for a moment, a girl comes to see me in the clinic. She used to speak but has experienced a loss of language, she has no social interactions, she has stereotypic behaviors. We evaluate her using ADOS (The Autism Diagnostic Observation Schedule – a standardized protocol for assessing social and communicative behavior) and the ADIR (Autism Diagnostic Interview-Revised) and the child fulfills all the criteria for an autism diagnosis. Yet she has a MECP2 mutation. What do you put in her chart? It can’t sayMECP2 mutation because that is not a clinical diagnosis, it’s a genetic one.

MC: Of course we are already facing these complicated issues. And I think the proposed changes in the DSM may further complicate things. As you can imagine, I’ve received a plethora of emails and phone calls from parents who are wondering what this may mean for their child in terms of losing services. I think worries about losing medical services are probably not warranted. Worries about educational services, however, I’m much more concerned about. For example, it may become more difficult to obtain intensive ABA (applied behavioral analysis) programs and other educational supports where autism has blazed a trail.

HZ: Yes, I would agree with that prediction. It is really important to remember that autism spectrum disorders do not only overlap clinically but that some of their features respond to similar therapies in spite of different molecular causes. Therefore keeping an eye on the clinical similarities in face of genetic heterogeneity is one path to gain insight about the mechanisms underlying their common features and to develop therapies that might benefit more than one disease. I do hope the committee will take these far-reaching ramifications into account as they contemplate disease classifications.

MC: Thank you so much for sharing these thoughts with our readers. Parents and other advocates for those with Rett Syndrome, such as therapists, teachers or personal physicians, are encouraged to weigh in on this matter. Remember, the cut-off date for submitting comments to the committee is April 20.