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Isabelle Rapin: Lessons from my clinic

by  /  24 May 2011

Full physical: Clinicians should test children for hearing impairments before they diagnose them with with autism, cautions Isabelle Rapin.

Why is the clear-cut, yes-or-no diagnosis of an autism spectrum disorder so difficult?

There is much disagreement among experts about borderline cases of autism, precisely because it is behaviorally defined and lacks — and will continue to lack — a test that provides a definitive answer.

Autism is diagnosed based on the severity and variety of its symptoms — in other words, its symptoms mimic height, weight, blood pressure or blood sugar, which are dimensional. In each, the cut-off between yes and no, or affected and normal, is based on agreement among experts and not a specific test — such as an X-ray that shows a fractured bone. You or I would be diagnosed as giant, dwarfed, obese, hypertensive or diabetic depending on how far from average we are on these measures.

No one disagrees with or doubts the diagnosis if the measure is very far from average, but there is a wide gray area at the edges of both normality and disease. This is also the case for many other developmental disorders, such as language delay, attention deficit hyperactivity disorder and intellectual disability. This makes diagnosing autism very difficult and easy to confuse with these and other disorders.

Especially in the days before autism was all over the Internet and print media, parents who came for advice were most likely to report problems with language: Either their preschooler’s language was delayed, or it had ceased to progress, had deteriorated, or even disappeared. Parents told us that it was usually between the ages of 15 to 30 months — occasionally even earlier — that they had become aware of the delayed language, plateau or regression.

Awareness of this problem was rarely sudden, but had occurred over several weeks, so that it often escaped attention — sometimes for months. To make matters worse, pediatricians frequently reassured parents, telling them that development can progress in leaps and starts or that little boys are likely to speak later and not as clearly and eagerly as little girls do.

Often it was a nursery school teacher, a speech pathologist friend, a grandmother or the worried parents themselves who pushed for an investigation that brought them to my office. At the time, parents’ main worries were intellectual deficiency or a developmental disorder limited to language. I would bring up two additional concerns: hearing loss or an autism spectrum disorder (ASD).

A glaring example:
Quite recently, I saw a lovely 3-year-old girl whose language was clearly deficient. Her nursery school teacher brought up the question of an ASD (this suspicion indicates how much better teachers are educated about autism than they were in the past). The child was very cute, intelligent and did not respond reliably when called by name, a frequent feature of children with autism. She related well to her parents and I was able to engage her in playing ball, neither of which is sufficient to rule out a diagnosis of ASD.

I spent a lot of time discussing diagnostic dilemmas, until I realized that I hadn’t asked whether the parents had an audiogram, or formal hearing test, to show me. The child had passed the newborn screen and the test had not yet been performed. The next phone call from this family reported that she had a significant hearing loss, especially for the high-pitched sounds critical for differentiating one consonant from another, and thus for language development.

As you can imagine, this cute little girl was promptly fitted with hearing aids, which she readily accepted, and the diagnosis of ASD flew out the window — her hearing loss is caused by an inner ear problem; it not currently severe enough to contemplate a cochlear implant, although we do not yet know whether it is progressive or not. The lesson is that prompt and competent hearing testing must be number one on the agenda for any child in whom there is a concern about language development, and must never be neglected. It must be performed even if the child appears to be hearing and needs to be repeated if language deteriorates.

(I will discuss in a future article how to distinguish developmental language disorders from an ASD).

Diagnostic difficulty:
These days, Internet-savvy parents worry about autism but do not always tell me their concerns when they visit my office, because they want to hear my independent diagnosis. Let me emphasize that autism is a behavioral diagnosis for which there is no biological test.

The importance of genetics has come to the forefront. Well over 100 different genetic mutations and other chromosomal abnormalities are known. But the key diagnostic dilemma is that, with some exceptions, virtually all these same gene variants or conditions can be found in healthy people.

There is also no prenatal diagnosis for behaviorally-defined autism, only for some neurological conditions that may be associated with autism — such as fragile X syndrome and Rett syndrome, and a small number of severe metabolic illnesses such as phenylketonuria, and malformations such as Joubert syndrome.

In the majority of individuals with an ASD for whom there is no obvious physical or neurological abnormality, multiple different genes probably contribute to the clinical picture. Knowing about these genes is useful to scientists trying to understand some of the biochemical or metabolic differences in the cells of people with autism, and may enable them to develop effective, scientifically-based medications.

But these differences will not determine whether the diagnosis of autism is correct. They will not be able to predict whether individuals with these genes will definitely have the group of symptoms we call autism. Differences in cellular metabolism may indicate that a person is at higher risk for autism, but not necessarily that a behavioral difference will be severe enough for a diagnosis of ASD.

What to do:
Most schools cannot deal with fuzzy dimensional diagnoses.

In order to assign Paul to an enclosed classroom with only eight children, a specialized teacher and aides, he needs to be categorically diagnosed as unequivocally having autism and being severely affected — regardless of the biological cause of his ASD. Another child on the spectrum with adequate language and IQ may be assigned to a class for typical children, yet be provided an aide if his behaviors are sufficiently handicapping. But he could also ‘lose his diagnosis’ and the extra help if his social skills are adequate. Such changing diagnostic labels and services are the result of being forced to assign categorical labels for what are dimensional deficits of variable severity.

Parents and teachers — and especially financially-strapped school districts — often ask for medication to minimize the expenditures associated with coping with such children’s behaviors. A review of medications widely prescribed for children with ASD concludes that only two fulfill research criteria for efficacy. And those two help only with aggressive behaviors, and have troublesome side effects1. A companion review indicates that the most effective intervention is intensive individualized intervention starting at the earliest possible age2.

These findings agree with my longstanding clinical experience. Knowing that no medical treatment is curative, as a neurologist I worry about potential long-term consequences of psychotropic medications and advocate for behavioral management, which, although more expensive, may help the child learn and permanently alter his brain development.

Lessons learned:
Autism has come a long way since I entered this field half a century ago. We have done away with the theory of refrigerator mothers. We know that autism spectrum disorders are disorders of the developing brain and have learned that genetics plays a major — but by no means exclusive — role in their cause. We are aware that epilepsy is linked to autism in ways we do not yet understand fully, but that it needs to be treated vigorously, especially if it occurs in infants and toddlers.

We need much more neurological, and genetic information, even though at present it rarely leads to a change in management of the child or provides firm genetic counseling for the family.

We are convinced that massive and expensive tests such as imaging, electrophysiology and genetics are almost always uninformative clinically, unless there are features that raise the suspicion of a diagnosable condition.

Families deserve the credit for major steps forward, because they banded together to insist that the results of such tests be collected and stored in large data banks accessible to researchers. Parents got the ball rolling by raising money and persuading the National Institutes of Health and the research community that autism spectrum disorders were crying out for investigation and for novel educational and medical treatments.

I salute them and anticipate that we can make much more progress if we can find the means to sustain the momentum of the past decade.

Isabelle Rapin is professor of neurology and pediatrics at the Albert Einstein College of Medicine in New York.


  1. McPheeters M.L. et al. Pediatrics Epub ahead of print (2011) PubMed

  2. Warren Z. et al. Pediatrics Epub ahead of print (2011) PubMed

5 responses to “Isabelle Rapin: Lessons from my clinic”

  1. Anonymous says:

    I highly appreciate your work and thanks for your tremendous work experience in the field as well. I agree that the cause of autism is linked with varied parameters, the branches of which are from sociological environment to bodily behavioural changes.
    Could I humbly ask myself that like the discovery of the Pencilline,the discovery of product (The name of the medicine? or treatment?) for curing autism would bring the wonder to us very soon? Thank you for giving me an opportunity to comment.

  2. Anonymous says:

    Hi, I finally heard of someone who has been in the field for nearly 50 years. My son is autistic but was given the diagnosis of PDD when he was little, she never explained what that was. He was given the diagnosis of EMH by the school system, 29 years ago. I have a hard time getting any help for him because he was not diagnosed autistic, he has many of the characteristics, I worked around autistic kids.Can he be diagnosed as an adult???

  3. Anonymous says:

    PDD is the umbrella term coined for the DSM III of 1980 to encompass 5 behaviorally-defined developmental disorders of childhood still in effect today:
    1) Autistic disorder, classic autism, the most severe subtype, apparent before age 3 years; 2) Asperger syndrome, the least severe; 3) PDD-NOS, i.e., autistic-like but doesn’t fulfill all criteria, or autistic traits or features, must have impaired sociability; 4) disintegrative disorder, a catastorphic regression after fully normal early development, including language; 5) Rett syndrome, a specific genetic disorder with autistic features at least at some point in time.

    PDD was used at the time because autism was thought to imply a hopeless untreatable condition, which turned out to be wrong for a large proportion (but not all!) affected individuals. Implies core deficits in A ) sociability; B ) communicative language, imagination/play; C ) repetitive movements, behaviors, or speech, rigidity, narrow interests.

    At present, autism spectrum disorders(ASD — autism for short) is favored to classify at the level of symptom description (like DSM) to indicate a wide range of severity and specific symptoms in different individuals. (It should not include Rett, which is one among many hundreds of genetic causes of ASDs. What to do about disintegrative disorder is undecided).

    Today we know that autism is not a single disease because it has many different causes —> “the autisms” at the level of causation (etiology). Most of the cases are multigenic, some single gene defects modified by other genes, some causes are environmental, but most have both genetic and environmental influences. Autism is a disorder of brain development that affects many levels: molecules and molecular networks, brain cells and networks between them, anatomy and physiology of different areas of the brain and their interconnections. Genes and other etiologies do not cause autism, their hierarchical effects involve many processes that underlie brain function in ways that affect function of individuals insimilar but never exactly identical ways.

    The diagnosis of autism is not biologic but behavioral. Yes there are criteria, mostly historical, to make a retrospective diagnosis. Anyone diagnosed as PDD or PDD-NOS as a young child would now be called Autism Spectrum Disorder and it may be possible to specify, which of the 4 disorders under the umbrella it fitted best.

  4. Anonymous says:

    Dr. Rapin offers a wise and clear view of autism diagnosis and treatment. I do take some issue with her downplaying the importance of genetic testing. In one paragraph she indicates that we need more genetic testing. In the subsequent paragraph she speaks out against genetic tests. In both paragraphs she downplays the potential value of these tests.

    Let us look at the value of genetic testing. In some cases the genetic tests reveal one or more causal (or risk factor) genes. Currently, there are over 100 genes that are identified risk factors. Many parents find solace in a genetic explanation. Solace is of great value and otherwise very hard to find in the autism world. In some cases, like mine, the information has serious consequences. In my case, I have an inherited balanced translocation of 22q13.3 (with 19q). This means that I am a carrier of a highly penetrant syndrome (Phelan-McDermid Syndrome) and that my children can be carriers, as well. I have traced this condition 5 generations back and spent years finding, warning, and testing family members for this rare, but severe condition. To date, we know Phelan-McDermid Syndrome frequently causes autism. We don’t yet know how often, since most identified cases are of very young children. Finally, as “uninformative” as genetic testing can be for any single individual, testing can be hugely informative to the greater community. “Massive tests” are not as expensive as they once were. Compared to the cost of caring for a person with autism, the cost of gene chips has become dirt cheap. Even the price of gene sequencing is plummeting. With the recent discovery that rare forms of autism (like Phelan-McDermid Syndrome) inform the protein networks of idiopathic autism (i.e., work of Huda Zoghbi), all those Phelan-McDermid Syndrome families who have sought “massive tests” and entered the results into the Phelan-McDermid Registry have brought us closer to better understanding and better treatments for all of autism.

    I recognize the article was aimed at the more practical side of autism and it does a wonderful job at helping parents approach decision making in an informed and practical way. But, it is a disservice to downplay the value of genetic testing. When Dr. Rapin speaks to a young family struggling with an autism diagnsis, I am sure she is thinking 20 or 30 years into their future. When she speaks of the value of genetic testing, I hope she considers the very practical value — born out 20 or 30 years from now through science and medicine — of that testing. The very pratical value is not only to family being tested, but also to all the subsequent families who will have to walk that same road.

    Andy Mitz
    Father of a son with Phelan-McDermid Syndrome

  5. Anonymous says:

    Thank you for informing me about one of the 100 genes of major effect on the risk of autism. I have not seen a case in 50 years in the field of pediatric neurology. Even though highly penetrant it must be exceedingly rare. I state in my piece that I am strongly in favor of a clinical genetic consultation and microarray testing under two circumstances: if testing is indicated clinically because the child has a family history or some features that suggest a diagnosable syndrome (even if I have no idea of what the syndrome might be)—testing would be indicated on clinical grounds whether or not the child is on the autism spectrum—or for research provided it is paid for by research funds. You may not be aware that a lot of testing for the benefit of the physician is performed and paid for by parents out of pocket, insurance companies or Medicaid, and I consider this dishonest. Every day we read in the New York Times of the juggernaut rise in the cost of medical care and physicians have to think twice about expensive clinical tests and treatments ordered routinely in the face of a miniscule chance of being of benefit to the patient. This is often put in the context of how many negative tests or operations must be obtained to save one affected person, or to give that person a few months of remission at the cost of thousands of dollars. I am well aware that patients and the parents of children with serious undiagnosed conditions do not want to think in terms of medical rationing, because that is what its unvarnished name is. There is no exact answer and will never be. I feel particularly strongly about futile attempts to keep elderly patients alive at all costs, even if I or my husband is that person and we have both made this clear to our children.

    You make a very good point about the relief the definite diagnosis a genetic test confers to the family, and that it results in savings because searching for an explanation for the unexpected illness without a name is no longer needed. We are at the beginning of huge progress in clinical and research genetics. What I am likely to say to the many parents of such a child is that the likelihood of finding a medical treatment or diet that will help the child is not zero but very close to it, that genetics isadvancing rapidly so that, if the child is young and the parents do not intend to have more children, there is a real advantage to waiting for more advanced testing methodology. Most crucial, I insist the child needs to be reevaluated by one appropriately trained physician after a specified time period, or earlier in case they or others have noted new symptoms. The disorder may be becoming more evident with maturation, or research progress relevant to their child has been reported. Some parents accept this program, I am sure others do not. Some times I end up compromising my view, but not always. Honesty and a frank discussion of the issues by both parties is essential for building long term trust, I have found. A number of parents have called me when their child was terminally ill and have donated tissue because they understood how much new knowledge parents and researchers need, and that their child was making a gift to society no healthy child could.

    Thank you for your sensitive and useful comments and I hope a favorable future for your family.

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