Rett syndrome: a class apart


Rett syndrome has long been linked to autism. So why is it now being re-classified away from the autistic spectrum?

Rett syndrome is a complex neurological disorder. Genetic in origin, it affects approximately one in 10,000 females and very few males. Although signs of Rett syndrome may not initially be obvious, it is present at birth and becomes more evident during the second year. People with Rett syndrome are profoundly and multiply disabled and need a high level of support throughout their lives.

The past fifteen years has seen many advances in Rett syndrome research, from the identification of genes causing Rett syndrome, through the partial reversal of symptoms in mice, to the exploration of glia and gene therapy. Despite this international progress, there are still an estimated 2,500 people living with Rett syndrome in the UK today. They desperately need effective diagnosis and support to ensure that they achieve the best possible outcomes throughout their lives.

Rett syndrome is about to be reclassified in the new American diagnostic system, DSM-V. Many parents are concerned about the implications of this for their daughters and about why the change is taking place. This article should help answer some of the questions and concerns.

A new system

Doctors are fairly methodical creatures, and to give some order to their world, they like to be able to neatly classify the diseases that they see. There are currently two main classification systems in use:

  • The International Classification of Diseases (ICD). This classification covers all diseases that we encounter across the field of medicine and, as its name suggests, it is used internationally. The current version is ICD-10. This will be replaced in 2015 by ICD-11
  • The Diagnostic and Statistical Manual of Mental Disorders (DSM). This is the system for diagnosing mental and psychiatric disorders in the United States. The current version is DSM-IV. This will be replaced in May 2013 by DSM-V.

In the UK, we use both DSM and ICD. Although there are some differences in approach, for individual disorders like autism and Rett syndrome the two systems are quite similar in the diagnostic criteria that they use.

In DSM-IV, “Rett’s Disorder” is an official diagnosis within the family of autism spectrum disorders. In DSM-V it is planned that Rett syndrome will be removed from the autism group. In fact, the recommendation is that it will be removed altogether from DSM-V. To understand the rationale for this, it is important to understand a bit more about the diagnosis and causes of autism.

Although a girl may have both autism and Rett syndrome, the two conditions are distinct.What is autism?

The most important thing to understand about autism is that it is not a single entity with a single cause. The word “autism” describes a package of behaviours that we may see in children, consisting of three main areas of difficulty:
Problems in social relatedness

These can range from very cut-off and aloof children (who were described when autism was first recognized by Leo Kanner in 1943) to children who are intellectually very able but who have difficulty in understanding more subtle social nuances. What is important is that the degree of social impairment is disproportionate to the intellectual capability of the individual; so, for example, you would not expect a person with normal IQ to ask if they can smell your shoes, but a person with autism may not see any problem in asking such a question.

Problems in communication
The hallmark here is not whether or not the child has verbal language; often s/he has quite fluent speech. The more particular problem is that the language the child has is not used communicatively. For example, a child with autism may be able to label lots of different items, but will not realize that s/he has to use that language to ask for a drink. Even a child without language can communicate well by pointing, shaking his/her head or eye pointing (looking at what they want and then back at their parent to indicate their choice). A non-verbal child with autism will not even use these physical means of communicating, because they do not understand the need to do so.

Restricted interests and stereotyped behaviours
Children with autism often insist that things are done in the same way, or they may have obsessional interests or topics of conversation. To make matters worse, because of the social relatedness problem, they will have no idea that their listener is completely bored by hearing endlessly about 1930s postage stamps or whatever it is that has captured their interest. It now becomes clear that a few autistic traits can sometimes be helpful, for example, if you are faced with the task of sitting down to rewrite the entire system for the classification of diseases. Along with the obsessions and/or repetitive behaviours, children with autism often have stereotyped behaviours such as hand-flapping, twirling or tapping on things.

What causes autism?

Children can arrive at this package of autistic behaviours through many different routes, but there are two broad groups:

  • in the majority of cases no single cause can be identified, although we know there can be a genetic predisposition. This is like having heart disease running in the family; not everyone will get it, but if you have a strong family history, you have more chance than the average person on the street
  • in a smaller number of children (currently about 15 per cent), there is a definite specific medical condition that has caused the autism. Each of the medical conditions that can cause autism is individually quite rare, but together they make up quite a large number of children. Examples are phenylketonuria, fragile X syndrome and tuberous sclerosis. Even a small proportion of children with Down syndrome can have autism, even though this is a condition in which individuals are more usually very friendly and chatty.
  • So, in the world of autism, diagnosis is at two levels. Firstly, does the child have autism? This question is answered by taking a careful description of his/her behaviours and observing him/her in clinic and sometimes in a more natural situation with peers (perhaps in school). Secondly, if the child does have autism, is there an identifiable medical cause? What this may mean in practice is as follows:
  • Charlie has autism. His brother has a language disorder, and his uncle was always thought to be a bit eccentric and lives alone. No medical cause has been found for Charlie’s autism.
  • Joe has fragile X syndrome. He has some learning disabilities, but is very sociable and does not meet criteria for an autism diagnosis. He has a cousin with Fragile X who also has autism.
  • Megan has Down syndrome, but she is not like any of the other children in her Down syndrome group. Her progress is slower, she does not interact with any of the other children and she spends much of the time playing repetitively in the sandpit. Megan has Down syndrome and autism.

Classifying Rett syndrome

When Rett syndrome was first described, people did not understand what caused it. They observed girls in their regression phase when they were often at their most cut off and withdrawn. They saw that, like many autistic children, they had some language and then lost it. They also noted that they had stereotyped hand movements. It is not difficult so see why they would have decided that this was a form of autism. However, even in making this diagnosis, they could see that girls with Rett syndrome were different from the majority of other autistic children, so they put them in their own little subgroup:

DSM-IV: Pervasive Developmental Disorders (Autism Spectrum)

299.00        Autistic disorder
299.80        Pervasive developmental disorder, not otherwise specified
299.80        Asperger’s syndrome
299.80        Rett’s disorder
299.10        Childhood disintegrative disorder

Now that it is clear that Rett syndrome is a biologically caused condition in its own right, it no longer makes sense to have it as a type of autism. However, like many other conditions, it can be a cause of autism.

We now know that once girls are out of the regression phase, their social interest and interaction can be amongst their strongest skills, even though their ability to communicate may be very limited. We also know that the hand stereotypies in Rett syndrome are neurologically driven rather than being something they choose to do; in fact, sometimes the stereotypies can interfere with them doing the things they want to do. So for many girls with Rett syndrome, it is not accurate to describe them as autistic, and may be counter-productive.

Rett syndrome and autism

As we have seen, someone with Rett syndrome can also have autism. Some girls with Rett syndrome will be less socially engaged, more motivated by toys than by people, and have other repetitive behaviours which are distinct from their hand wringing. Anecdotally, many clinicians in the field, such as Helen Leonard in Australia and our own team in the UK, have observed that we more frequently see this autistic picture in the mobile girls than in those who are non-walkers.

For these girls, a diagnosis of autism and Rett syndrome will be useful because it may dictate a different educational approach from those who do not have autism.


I think it is a good thing that Rett syndrome is coming out of the autism spectrum. It allows us to make a much more individualised assessment in each girl as to whether she has Rett syndrome and autism or just Rett syndrome, and to plan accordingly. If she does have autism, she should still be able to access relevant educational approaches.

Further information

Hilary Cass is Paediatric Neurodisability Consultant at Evelina Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust:

For more information about Rett syndrome, visit:

Hilary Cass
Author: Hilary Cass

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