Fragile X and Autism

Fragile X and Autism 2019-07-22T19:44:40+00:00

Fragile X & Autism

Individuals with Fragile X syndrome (FXS) are frequently co-diagnosed with autism (aka autism spectrum disorder, or ASD), and families and some professionals are often confused by the relationship between the two. Much of our understanding has so far come from family surveys and small studies, but larger studies—including those utilizing data from the NFXF FORWARD Registry & Database—emerging to help us better understand the impact of an autism diagnosis in the care of people with FXS, and whether the link between the two extends beyond behavioral similarities.

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.

—DR. RANDI HAGERMAN

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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.

—DR. RANDI HAGERMAN

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Diagnosing Autism

What is Autism?

Autism is a spectrum disorder, which means there’s a wide range of lifelong symptoms that vary in form and severity, but it is generally characterized by an impairment in social interaction and communication, and the presence of restricted and repetitive patterns of behavior, interests, or activities.

Symptoms first appear in early childhood, with studies showing that parents on average notice developmental problems before their child’s first birthday. According to the latest CDC findings, 1 in 59 children in the U.S. were diagnosed with ASD by age 8, and males are four times more likely than females to receive the diagnosis.

Causes of Autism

There is a strong genetic component to autism. For example, almost 20% of younger siblings of a child with ASD will receive a diagnosis themselves, which is much higher than the CDC-reported 1% to 2% risk among the general population.

Researchers continue trying to determine both the genetic and non-genetic environmental factors that contribute to autism—about 15% of children with ASD have been identified as having a genetic disorder, such as Fragile X syndrome, tuberous sclerosis, Down syndrome, or other chromosomal abnormalities, copy number variants, and single gene mutations. It is expected that as genetic testing becomes more sensitive, the percentage of individuals with a genetic cause will increase, however, non-genetic factors (such as exposure to a maternal immune response in the womb or complications during birth) have also been found to play a role

The Diagnosis

There is no medical test, such as a blood test or brain scan, to diagnose autism. Instead, a developmental or general pediatrician, neurologist, psychologist, psychiatrist, or other specialist, will look at a child’s behavior and development to determine both the diagnosis and its severity. The standard reference used to diagnose mental and behavioral conditions—including autism—is the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). There are also cases where a child does not meet the diagnostic criteria for autism, but will have autistic-like features.

Treating Autism

Early intervention services are important for children from birth to 3 years old, and include therapy to help the child interact with others. A parent suspecting autism or other developmental problems needs to work with their child’s doctor as soon as possible.

Treatments beyond early intervention fall into the categories of behavior and communication, dietary, medication, and complementary medicine, which may include:

  • Auditory training.
  • Discrete trial training.
  • Vitamin therapy.
  • Anti-yeast therapy.
  • Facilitated communication.
  • Music therapy.
  • Occupational therapy.
  • Physical therapy.
  • Sensory integration.
Learn More

A Blood Test for Autism? Not so Fast »
The notion that autism itself can be directly diagnosed through a blood test is incorrect and misleading.

FORWARD Registry & Database »
FORWARD is a first-of-its-kind longitudinal database of clinician- and parent-reported data from individuals living with FXS.

Diagnostic Tools
Diagnostic and Statistical Manual of Mental Disorders (DSM-5) »

Diagnosing Fragile X

What is Fragile X Syndrome?

FXS is a genetic condition that causes intellectual disability, behavioral and learning challenges, and various physical characteristics. Though FXS occurs in both genders, males are more frequently affected than females, and generally with greater severity. The agreed upon prevalence of FXS is approximately 1 in 3,600–4,000 for males and 1 in 4,000–6,000 for females.

No one individual will have all the features of FXS:

  • Behavioral characteristics include ADD, ADHD, social anxiety, hand-biting and/or flapping, poor eye contact, sensory disorders, increased risk for aggression, and autism and autistic-like behaviors.
  • Intellectual disabilities include a range from moderate learning disabilities to more severe intellectual disabilities.
  • Physical features may include large ears, long face, soft skin, and large testicles (called “macroorchidism”) in post-pubertal males.
  • Connective tissue problems may include ear infections, flat feet, high arched palate, double-jointed fingers, and hyper-flexible joints.
  • Disposition: They are very social and friendly, have excellent imitation skills, have a strong visual memory/long term memory, like to help others, are nice, thoughtful people and have a wonderful sense of humor.

Cause of FXS

Fragile X syndrome is caused by the expansion or lengthening of the FMR1 gene on the X chromosome, known as a gene mutation. The X chromosome is one of two sex-determining chromosomes. When the gene lengthens it switches off production of a protein that is involved in brain development and other functions. Learn more about FXS genetics and inheritance.

The Diagnosis

The FMR1 DNA Test (sometimes called the Fragile X DNA Test) is the standard of care for determining the presence of Fragile X. DNA testing detects more than 99% of individuals (both males and females) with FXS, as well as Fragile X premutation carriers.

Who Should Have Fragile X Testing?

Any male or female with intellectual disabilities, developmental delay, speech and language delay, autism or learning disabilities of unknown cause.

Any female with infertility, elevated FSH levels, premature ovarian failure, primary ovarian insufficiency, or irregular menses. Learn more.

Any male or female over 50 with features of FXTAS, including intention tremors, ataxia, memory loss, cognitive decline, or personality change, especially in combination with a positive family history of Fragile X.

Any preconception or pregnant female who expresses interest in or requests Fragile X carrier testing.

Learn more about Fragile X Testing. To locate a genetic counselor in your area, visit the National
Society of Genetic Counselors
, or contact the National Fragile X Foundation:
treatment@fragilex.org | (800) 688-8765.

Who Should Have Fragile X Testing?

Any male or female with intellectual disabilities, developmental delay, speech and language delay, autism or learning disabilities of unknown cause.

Any female with infertility, elevated FSH levels, premature ovarian failure, primary ovarian insufficiency, or irregular menses. Learn more.

Any male or female over 50 with features of FXTAS, including intention tremors, ataxia, memory loss, cognitive decline, or personality change, especially in combination with a positive family history of Fragile X.

Any preconception or pregnant female who expresses interest in or requests Fragile X carrier testing.

Learn more about Fragile X Testing. To locate a genetic counselor in your area, visit the National Society of Genetic Counselors, or contact the National Fragile X Foundation: treatment@fragilex.org | (800) 688-8765.

Treating FXS

There are many areas of treatment and intervention that can improve the lives of affected individuals and their families. Given the proper education, therapy, and support, all persons with FXS can make progress.

Traditional strategies for behavioral issues in children are less effective for decreasing inappropriate behaviors in individuals with FXS. Instead, a behavior plan that is “front-loaded” with antecedent strategies is recommended so that the person with FXS is supported and set up to engage in appropriate behaviors.

General treatment guidelines are centered around speech and language, feeding, anxiety (including social anxiety), hyperarousal, sensory sensitivities, ADHD, aggression, and self-injurious behaviors.

Interventions designed by a team with specific knowledge of the behavioral, learning, medical, and physiological characteristics associated with FXS are usually helpful in reducing challenging behaviors. Along with a proactive approach and appropriate accommodations, a solid intervention plan will likely foster positive outcomes and set up the child or adult for success.

Learn More

Treatment & Intervention »
Given the proper education, therapy, and support, all persons with FXS can make progress.

Behavioral Challenges in Fragile X Syndrome »
A consensus of the Fragile X Clinical and Research Consortium.

Fragile X Clinics »
Fragile X clinics provide individuals and families affected by a Fragile X conditions with comprehensive evaluation and treatment recommendations.

Autism + FXS

Among the genetic causes of autism, FXS—one of the more than 800 genes associated with ASD—is the most common known inherited single-gene disorder, and accounts for an estimated 1% to 6% of all autism cases, and according to the CDC, a national parent survey found that 46% of males and 16% of females with FXS have been diagnosed or treated for ASD.

46%
16%
46%
16%

According to the CDC, a national parent survey found that 46% of males and 16% of females with FXS have been diagnosed or treated for ASD.

Testing for Known Genetic Causes of ASD

Though blood tests are not part of an ASD diagnosis, they can and do come into play to rule out known genetic causes (though oftentimes, the cause remains unknown). Having a genetic diagnosis in addition to an ASD diagnosis can help families in several ways—most notably, it can alert them to other potential conditions, including FXS.

Autism and FXS (and other neurodevelopmental disorders) are often diagnosed separately, with many children diagnosed with autism before they are diagnosed with FXS. According to one study, it is “naïve and counterproductive” to assume that autism is the same in FXS as it is in autism alone, or that the same treatments will work in both cases. In other words: A child diagnosed with ASD would ideally be undergoing treatment for their autism. But if they also have undiagnosed FXS, that treatment would not take their FXS into account. For example, an impairment in social interaction is one of the core characterizations of autism. But since many children with FXS are interested in social interactions, treatments for ASD that focus on the social aspect, may not be productive in the overall care for those with FXS+ASD.

Because of the link between autism and FXS, pediatrician and Fragile X expert Dr. Randi Hagerman recommends that children diagnosed with autism receive a genetic evaluation and testing for FXS and other genetic causes.

Treating FXS+ASD

Challenging behaviors that are seen in a higher proportion of children with FXS+ASD vs. those with FXS alone, include attention problems, hyperactivity and impulsivity, anxiety, and aggressive and self-injurious behaviors.

The mainstay of treatment is behavioral therapy, but medication can sometimes also be helpful to support speech-language, occupational, and educational therapeutic services, and to allow a child to learn in the least restrictive environment.

More intensive speech/language therapy, with an emphasis on group sessions, behavioral therapy, and augmentative technology are often indicated for FXS+ASD, and young children should also have intensive therapeutic intervention through early intervention programs. Because of their relatively lower cognitive level, educational strategies may need to include as much focus on daily living skills as on academics.

Learn More

Autism Spectrum Disorder in Fragile X Syndrome: Cooccurring Conditions and Current Treatment »
This study examines the impact of the ASD diagnosis in a large clinic-based FXS population to better inform the care of people with FXS. (Pediatrics, June 2017, Vol. 139)

The Fragile X Syndrome–Autism Comorbidity: What Do We Really Know? »
This study looks at important differences in ASD symptoms between individuals with FXS+ASD and those with ASD alone. Also see Behavioral Issues in FXS+ASD, a summary and introduction to the study.

Q&A With Dr. Hagerman: Exploring the Fragile X Syndrome / Autism Link »
Fragile X expert Dr. Hagerman discusses the important link between FXS and autism, and new developments and treatments for both.

Fragile X Syndrome Testing & Diagnosis »
DNA testing detects more than 99% of individuals (both males and females) with FXS, as well as Fragile X carriers.

The Who, What & How for Genetic Counseling »
Who should seek counseling? What does a genetic counselor do? How do I find one?

Also See:
National Society of Genetic Counselors »

Similarities & Differences

FXS vs. ASD

Characteristics that have been found to differ between the FXS behavioral phenotype and ASD include:

  • The frequency of intellectual disability is higher in FXS than ASD. Most males and about a third of females with FXS have intellectual disability, while only about 40% of individuals with ASD have intellectual disability.
  • Motor coordination deficits are worse in FXS than ASD.
  • Individuals with autism are more likely to show worse receptive language than expressive language, while individuals with FXS tend to show the opposite pattern.
  • Interest in socializing is higher in FXS in general than ASD (although limited by anxiety and avoidance).
  • Imitation skills are better in FXS than ASD when level of intellectual impairment is controlled.

FXS+ASD vs. FXS Alone

Above we outlined descriptions of behaviors in common and different between the FXS behavioral phenotype and ASD. Characteristics of individuals with FXS who meet criteria for ASD (FXS+ASD) compared to individuals with FXS alone include:

  • Less developed language skills, particularly receptive skills.
  • Lower non-verbal cognition and IQ scores.
  • Lower adaptive skills.
  • More severe overall behavioral problems.
  • Reduced interest in and motivation for social interaction or a failure to attend to social information that might promote appropriate social behavior.

Consequently, from educational and vocational viewpoints, individuals with FXS+ASD face similar but more severe challenges than children with FXS.

Learn More

Clinical Insights into the Similarities and Differences for Diagnosis and Treatment »
The two conditions may have considerably more overlap than previously thought.

A Complex & Evolving Relationship

The relationship between FXS and autism is complex and constantly evolving, and despite the frequency and severity of autism in FXS, there are still important gaps in knowledge due to limited research, samples, and surveys.

For further reading on the relationship between autism and Fragile X syndrome, see Fragile X Syndrome Related Concerns on the CDC website, and related consensus documents and articles below.

Learn More

FXCRC Consensus Document “Autism Spectrum Disorder in Fragile X Syndrome” »
This document clarifies how the ASD diagnosis and FXS can overlap, and where they do not.

The Fragile X Family of Disorders: A Model for Autism and Targeted Treatments »
The two conditions may have considerably more overlap than previously thought.

Watch: Autism Spectrum Disorder in Fragile X Syndrome: An NFXF Webinar with Dr. Walter Kaufmann »
Dr. Walter Kaufmann presents, “Autism Spectrum Disorder and Fragile X Syndrome, Co-Occurring Conditions and Current Treatment.”