Autism and Fragile X Syndrome

What Is Autism?

Autism or autistic spectrum disorder (ASD) is a behavioral diagnosis. The range of symptoms in autism vary and are generally characterized by an impaired ability to communicate and interact socially with other people. Sometimes children will not meet the diagnostic criteria for autism but will have “autistic-like features.”

The diagnosis of autism is usually made by a developmental or general pediatrician, neurologist, psychologist, psychiatrist, or other specialist. The diagnosis is made after evaluating the child using a number of different behavioral tools and tests. There is no blood test for autism, and imaging studies such as MRIs don’t diagnose the condition; it is purely a behavioral diagnosis similar to ADHD, ADD, etc.

What Causes Autism?

Autism is caused by a number of different factors, some genetic and some non genetic. Much remains unknown about the condition—including what causes it in many individual cases. When a child is diagnosed with autism, blood tests are often ordered rule out the known genetic causes. Fragile X Syndrome is the most common known genetic (“single gene”) cause of autism. Other genetic causes include deletions of chromosome 15q, tuberous sclerosis, PKU and other rare genetic conditions.

Many times a child with autism will be tested or evaluated for all the known genetic causes of autism but no cause will be found. However, family studies have shown that in families with one child with autism there is an increased risk for another child to have the condition. This risk is not as high as in those families with an identified single gene cause, such as fragile X syndrome. It is more in line with “multifactorial” risks, similar to heart defects or cleft lip. This leads experts to believe there is a genetic component even in those without a “single gene” identified cause.

Many researchers are trying to determine both the genetic and non-genetic factors that contribute to autism.

Relationship Between Autism and FXS

Whereas autism is a behavioral diagnosis, fragile X syndrome (FXS) is a medical or more accurately, a genetic diagnosis. When associated with FXS, the autism is caused by the genetic change or mutation in the Fragile X gene. This is similar to other conditions such as Down syndrome. Individuals with Down syndrome can also have other conditions, including autism, hearing loss, diabetes and other behavioral and medical conditions. If a child is diagnosed with autism and then diagnosed with FXS, he or she still has autism, it is just that the cause of their autism is known. It is no different than someone with FXS also having ADHD or any other behavioral symptom of FXS.

The article FXS and Autism: Similar But Different highlights a well-attended panel discussion at the 13th International Fragile X Conference where they pondered the topic: “FXS and Autism: Clinical Insights into the Similarities and Differences for Diagnosis and Treatment.”

How Many Children With FXS Have Autism?

Many studies have evaluated the FXS-autism link over the past decade. These studies have shown the percentage of children with FXS who have autism varying from 15 to 33 percent. This range may be due to the fact that the diagnostic criteria for autism have varied and the diagnostic tools used have changed.

Since many children with FXS are interested in social interactions, they may not meet the diagnostic criteria for autism, even as they exhibit autistic-like features such as poor eye contact, shyness, social anxiety, hand-flapping and sensory issues. Autism is much more common in boys with FXS than in girls with FXS.

How Many Children With Autism Have FXS?

Approximately 2-6 percent of children with autism are diagnosed with FXS. Given the possibility of a link, it is recommended that all children with autism, both male and female, be referred for genetic evaluation and testing for FXS and any other genetic cause of autism.

Autism’s Effect on Children With FXS

Studies show that individuals with FXS who have autism can have a more significant intellectual disability (lower IQ) than those with FXS who do not have autism.

For further reading on the relationship between autism and fragile X syndrome, see:

  • The Fragile X Family of Disorders: A model for Autism and Targeted Treatments
    Abstract
    CGC-repeat expansion mutations of the fragile X mental retardation 1 (FMR1) gene are the leading known cause of autism and autism spectrum disorders (ASD). Full mutation expansions (>200 CGC repeats) of the gene are generally silenced, resulting in the absence of the FMR1 protein and fragile X syndrome. By contrast, smaller expansions in the premutation ragne (55-200 CGC repeats) results in excess gene activity and RNA toxicity, which is responsible for the neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), and likely additional cases of developmental delay and autism. Thus, the FMR1 gene is causative of a common (autism) phenotype via two entirely different pathogenic mechanisms, RNA toxicity and gene silencing. The study of this gene and its pathogenic mechanisms therefore represents a paradigm for understanding gene-brain relationship and the means by which diverse genetic mechanisms can give rise to a common behavioral phenotype.
  • Autism Spectrum Disorder in FXS: Communication, Social Interaction, and Specific Behaviors
    Abstract
    The present study extends our previous work on social behavior impairment in young males with fragile X syndrome (FraX). Specifically, we evaluated whether the autistic phenomenon in FraX is expressed as a range of behavioral impairments as in idiopathic autism (Aut). We also examined whether there are behaviors, identified as items of the Autism Diagnostic Interview-Revised (ADIR), that in FraX predispose to or differentiate subjects with autism spectrum disorder (ASD) diagnosis. Finally, regression models were utilized to test the relative contribution of reduced communication and socialization skills to ADI-R scores and diagnoses. A cohort of 56 boys (3–8 years)with FraX was examined in terms of scores on measures of cognition (IQ was a co-variate in most analyses.), autistic behavior, problem/aberrant behavior, adaptive behavior, and language development. We found that, indeed, in terms of problem behavior and adaptive skills, there is a range of severity from FraX + Aut to FraX + PDD (Pervasive Developmental Disorder) to FraX + none. ADI-R items representing “Play” types of interaction appear to be “susceptibility” factors since they were abnormal across the FraX cohort. Integrated regression models demonstrated that items reflecting complex social interaction differentiated the FraX + ASD (Aut + PDD) subgroup from the rest of the FraX cohort, while abnormalities in basic verbal and non-verbal communication distinguished the most severely affected boys with FraX + Aut from the milder FraX + PDD cohort. Models incorporating language, adaptive communication, and adaptive socialization skills revealed that socialization was not only the main influence on scores but also a predictor of ASD diagnosis. Altogether, our findings demonstrate that the diagnosis of ASD in FraX reflects, to a large extent, an impairment in social interaction that is expressed with variable severity in young males with FraX.
    © 2004 Wiley-Liss, Inc.
    KEY WORDS:
    fragile X; autism; autism diagnostic interview (ADI); social withdrawal; socialization; communication