Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that impacts a person’s ability to communicate and participate in both verbal and non-verbal social interactions. People with ASD can also exhibit a wide range of restrictive or repetitive patterns of behaviors. Intense focus on a single toy or TV show, repeated hand flapping, or the inability to transition from one activity to the next or to stray from an established daily routine are examples of restrictive/repetitive behaviors.

For over a decade, the Centers for Disease Control and Prevention (CDC) have collected data1 on the number of children diagnosed with ASD. In the most recent report of data collected in 2010, the CDC estimates that 1 in 68 children in the US have ASD. ASD is diagnosed in people from all racial, ethnic, and socioeconomic backgrounds, however it is more common in boys than girls, with a 5:1 ratio.

What causes ASD?
The causes of ASD are not well understood; however, it’s likely that both genetics and environment play a role. Studies on identical twins have found that if one twin is diagnosed with ASD, 62% – 90% of the time the other twin is also affected with ASD or a broader autism phenotype (does not meet clinical criteria for ASD but has significant communication or social deficits)2. Sibling studies have also shown that siblings of a child with ASD have a 10% risk of developing ASD and a 20% risk of developing the broader autism phenotype3.

Despite the increase in awareness, diagnosis, and research, there is still no diagnostic blood test specifically for ASD. In fact, a genetic cause is only identified in about 23% of ASD cases.

The types of known genetic mutations that have been associated with ASD are:

  • Single gene disorders (~15%) include conditions such as fragile X syndrome and tuberous sclerosis. Fragile X syndrome is the most common cause of inherited intellectual disability and the most common known single gene cause of ASD. Approximately 2-6 % of children with ASD are also diagnosed with fragile X syndrome5.
  • Copy number variants (CNVs) (~5-10%) are small extra (duplications) or missing (deletions) pieces of chromosomal material. There have been hundreds of CNVs associated with ASD. One of the more common CNVs associated with ASD is 16p11.2 and it has been seen in ~1% of cases of people with ASD6.
  • Chromosome abnormalities (~3%), also known as aneuploidy, are missing or extra whole chromosomes. Common aneuploidies that are compatible with life are Turner syndrome, Klinefelter syndrome, and Down syndrome, all of which have an increased association with ASD.

How is ASD diagnosed?
An ASD diagnosis typically requires a cross-specialty approach, including but not limited to: primary care physicians, developmental pediatricians, neurologists, and psychologists. In 2013, the American Psychiatric Association revised the criteria by which ASD is diagnosed in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. The following criteria are required to diagnose ASD6:

A. Persistent deficits in social communication and social interaction across multiple contexts, as manifested by the following, currently or by history:

  1. Deficits in social-emotional reciprocity, ranging, for example, from abnormal social approach and failure of normal back-and-forth conversation; to reduced sharing of interests, emotions, or affect; to failure to initiate or respond to social interactions.
  2. Deficits in nonverbal communicative behaviors used for social interaction, ranging, for example, from poorly integrated verbal and nonverbal communication; to abnormalities in eye contact and body language or deficits in understanding and use of gestures; to a total lack of facial expressions and nonverbal communication.
  3. Deficits in developing, maintaining, and understanding relationships, ranging, for example, from difficulties adjusting behavior to suit various social contexts; to difficulties in sharing imaginative play or in making friends; to absence of interest in peers.

B. Restricted, repetitive patterns of behavior, interests, or activities, as manifested by at least two of the following, currently or by history:

  1. Stereotyped or repetitive motor movements, use of objects, or speech (e.g., simple motor stereotypies, lining up toys or flipping objects, echolalia, idiosyncratic phrases).
  2. Insistence on sameness, inflexible adherence to routines, or ritualized patterns in verbal or nonverbal behavior (e.g., extreme distress at small changes, difficulties with transitions, rigid thinking patterns, greeting rituals, need to take same route or eat the same food every day).
  3. Highly restricted, fixated interests that are abnormal in intensity or focus (e.g., strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interest).
  4. Hyper- or hypo-reactivity to sensory input or unusual interests in sensory aspects of the environment (e.g., apparent indifference to pain/temperature, adverse response to specific sounds or textures, excessive smelling or touching of objects, visual fascination with lights or movement).

C. Symptoms must be present in the early developmental period (but may not become fully manifest until social demands exceed limited capacities, or may be masked by learned strategies in later life).

D. Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning.

E. These disturbances are not better explained by intellectual disability (intellectual developmental disorder) or global developmental delay. Intellectual disability and autism spectrum disorder frequently co-occur; to make comorbid diagnoses of autism spectrum disorder and intellectual disability, social communication should be below that expected for general developmental level.

In 2013, the American College of Medical Genetics and Genomics (ACMG) issued practice guidelines for the clinical evaluation of the genetic causes of ASD7. Based on what is currently known about common genetic causes of ASD, ACMG recommends the following as a first tier approach for evaluating a person with a suspected diagnosis of ASD:

  • Obtain a family history
  • Chromosomal Microarray Analysis (CMA) – also known as Comparative Genomic Hybridization (CGH). CMA detects DNA changes in greater detail than a karyotype. CMA is one way to detect CNVs that are commonly seen in individuals with ASD. However, CMA can only detect missing or extra genetic information. Translocations, where the total genetic material is present but rearranged, cannot be detected.
  • Fragile X testing of the FMR1 gene. This test is done to look for repeating DNA segments within the FMR1 gene, present on the X chromosome.

Is preconception/prenatal testing available for ASD?
Unfortunately there is no specific test that is recommended for routine screening prior to or during pregnancy that can determine a risk for all ASD. Carrier screening for fragile X syndrome can provide information about the risk to have a child with fragile X syndrome.

If there is a specific increased risk based on a family history (e.g., a previous child or sibling diagnosed with ASD), testing the affected individual could provide the most information about a possible genetic risk to future pregnancies. A genetic counselor can also help provide information about empiric risks as well.

References for additional information about ASD
Autism Speaks
Simons Foundation Autism Research Initiative
National Institute of Mental Health

To find a genetic counselor, visit the National Society of Genetic Counselors at


  1. Centers for Disease Control and Prevention. (2014). Data and Statistics. Retrieved from
  2. Muhle R, Trentacoste SV, Rapin I. The genetics of autism.  Pediatrics. 113(5):e472-86 (2004).
  3. Constantino JN, Zhang Y, Frazier T, Abbacchi AM, Law P. Sibling recurrence and the genetic epidemiology of autism.  Am J Psychiatry. 167(11):1349-56 (2010).
  4. Guo H, Hu Z, Zhao J, Xia K. Genetics of autism spectrum disorders. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 36(8):703-11 (2011).
  5. National Fragile X Foundation. (2012). Autism and Fragile X Syndrome. Retrieved from
  6. Autism Speaks (2013). DSM-5 Diagnostic Criteria. Retrieved from
  7. Schaefer GB, Mendelsohn NJ. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genetics in Medicine. 15, 399–407 (2013).

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