Genetics of Autism Spectrum Disorder (ASD)

Read Part One: Autism Spectrum Disorder

Collaboratively written and edited by: Joan Kornkven, Megan Lew, Rachel Baer, Mark Schmertmann, MSW, LSW, and Andy McCarty, MS, CGC

 

SUMMARY: ASD is complex, but a better understanding of how it presents has increased earlier diagnoses and has allowed more people with ASD to be recognized (12). The increase in prevalence means schools and clinics need to be better equipped to help those with ASD. Under the 1975 Individuals with Disabilities Education Act (IDEA), states must provide children with an education that meets their individual needs (13). Schools must legally provide any accommodations that a child needs, however, they do not need to provide the most optimal or best choice. It is important to advocate for individuals with ASD to get the best care possible as early as possible. At the same time, a better understanding and awareness of ASD would decrease its stigma and allow for ASD to be seen as a difference that requires non-traditional approaches within education, healthcare, and daily living rather than a disorder.

 

Clover Genetics can provide genetic counseling for those with diagnosed or suspected ASD as well as facilitate genetic testing reviewed by both a genetic counselor and a physician. We offer post-test counseling to discuss the results and provide answers to questions, resources, and support for each patient.

On This Page:

  • Definitions

  • Genetic Components of ASD

  • The Role of Genetic Testing

  • Genetic Testing for ASD

  • Is Genetic Testing Controversial?

  • Citations

Important Definitions:

Autism Spectrum Disorder (ASD)

A developmental disorder of variable severity that is characterized by difficulties in social interaction and communication and by restricted or repetitive patterns of thought and behavior (14).

Neurotypical

People with typical neurological development or function; Those who do not display or experience characteristics of neurologically diverse patterns of thought or behavior like: Autism Spectrum Disorder (ASD), Attention Deficit Disorder / Attention Deficit Hyperactivity Disorder (ADD/ADHD), Obsessive Compulsive Disorder (OCD), or other neurological or neuropsychiatric differences are considered neurotypical (14).

Neurodivergent

People who display or experience characteristics of neurologically diverse patterns of thought or behavior like: Autism Spectrum Disorder (ASD), Attention Deficit Disorder / Attention Deficit Hyperactivity Disorder (ADD/ADHD), Obsessive Compulsive Disorder (OCD), or other neurological or neuropsychiatric differences are considered to be neurodivergent (14).

Assigned Male/Female At Birth (AMAB or AFAB)

The sex (male or female) assigned to a child at birth, which is most often based on the baby’s external anatomy (15). This is separate from the construct of gender and is strictly based on the doctor’s initial impression of the baby’s sex at birth.

Non-speaking

A descriptor for a person who either does not learn how to speak, is unable to speak, or is uncomfortable speaking for any reason including neurologic underdevelopment, traumatic brain injuries, or other physical conditions, like problems with the vocal cords (16).

Non-speaking Autism

A person with ASD who does not speak or only speaks with few words. Some people with ASD prefer to utilize alternate forms of communication because they find communicating through speech to be more difficult even if they are physically capable of speech. Some affected individuals write and verbally communicate in other ways such as typing or through special communication devices. Non-speaking individuals are generally still able to comprehend language (17).

Genome

The complete set of genes or genetic material present in a cell or organism (14). This includes the genetic material that codes for genes. Genes are responsible for making the proteins that help us to function. The genome includes non-coding genetic material that does not code for genes, but rather regulates the activity level of the genes and plays other roles.

Exome

The part of the genome that includes DNA that codes for proteins, or genes. These coding genes are in groups called exons, which are the only thing included in the exome (18).

 

Genetic Components of ASD

Studies over the last decade have pointed to random genetic changes that alter specific proteins important to neurodevelopment as responsible for about one-quarter of ASD cases (6). However, there are over 1,000 identified genes associated with an increased risk for ASD, so genetic testing is rarely the first approach to diagnosis and most cases of ASD do not have a confirmed genetic cause (5). Instead, non-invasive ASD Screenings are usually performed by a pediatrician as they monitor a child’s development. Adults can also undergo non-invasive ASD screenings with specialists, like their primary care physician, neurologist, or psychiatrist (19). 

Keeping in mind an increased risk does not mean a person automatically has the syndrome, environmental risk factors can combine with an increased genetic likelihood for ASD. Examples of environmental risk factors that may increase the chances of an ASD diagnosis include:

  • advanced parental age at conception,

  • complications at birth,

  • having a sibling or parent already diagnosed with ASD (5).

While genetic factors may contribute between 40-80% to the likelihood of having ASD, it is important to keep in mind that an increased risk does not necessarily mean that a person will have the syndrome and, currently, most cases do not have an identifiable genetic change as the specific cause of the disorder (5). However, with modern genetic testing, the knowledge of specific genetic changes can provide those with a genetic diagnosis of ASD, which can provide more personalized or targeted treatment options associated with symptoms of their individual genetic changes (1, 19). This is not intended to “cure” an individual’s neurodivergence, but rather, to address possible unwanted symptoms or side-effects caused by specific genetic changes that may cause neurological complications like seizures, anxiety, depression and others (19).

Just as there are many presentations of symptoms in ASD, those symptoms stem from multiple genetic factors rather than one single genetic change. While definitive genetic diagnosis is not always possible, about 2-4% of ASD cases that undergo genetic testing identify a specific genetic or chromosomal change as the primary cause of ASD (5). These genes play a role in neurological development, so genetic changes in these regions, or sometimes in the regulatory regions of DNA supporting the gene, can have a crucial impact on brain development and possibly result in syndromes like ASD (5, 6).

Some examples of important genes with rare genetic changes linked to ASD include:

  • ADNP,

  • ARID1B,

  • CHD2,

  • POGZ,

  • SHANK3,

  • SYNGAP1 (5)

 
 

The Role of Genetic Testing

Genetic testing of children and adults suspected of having, or diagnosed with ASD has allowed for genetic researchers to study the role of various genes in neurological development. While genetic testing can be used to give answers to families and contribute to future research, fewer than half of people with ASD get genetic testing (7). This makes sense, as the primary way for diagnosing ASD has been through specialist-provided diagnoses, whereas modern genetic testing is more expensive and many people- patients, families, and physicians alike, do not understand any potential benefits of genetic testing for ASD, or, are more concerned with the risks.

Genetic testing can offer peace of mind to people and families with ASD because it validates and explains their experience with neurodivergence. Outside of the possibility of confirming a person’s lived experience, genetic testing can also be valuable for patients with ASD because some genetic variants that cause ASD are linked to other health conditions (8). Identifying if a patient with ASD has any unknown genetic medical risks prevents delays to accessing further valuable care and can also inform family members of their potentially shared risk.

Without genetic testing, individuals and families cannot know if there is a genetic change running in their family. Further, when providers know that an individual is at high risk for a certain disease, they can better implement the correct screening to decrease the chance of serious illness. Gaining this information earlier in life can be especially helpful for people with nonverbal ASD who may not be able to easily advocate for themselves or possibly cannot self-report symptoms. In these cases, genetic testing beyond diagnosing ASD can be particularly valuable during regular preventative care for high-risk hereditary cancer syndromes, which dramatically increase a person’s likelihood of developing cancer and can only be confirmed through genetic testing.

However, genetic testing for ASD can often be difficult to receive even for those interested. Adult genetic testing for ASD may not be covered by insurance, but the costs associated with adult genetic testing may be worth it for people struggling to determine the cause of their symptoms. Some may opt to get an evaluation by a specialist who can diagnose ASD with neuropsychiatric testing rather than genetic testing, but finding the appropriate specialists to offer the correct testing is often difficult for patients.

 
 

Genetic Testing for ASD

The current standard genetic test for ASD is called a microarray, which has been demonstrated to identify a genetic variation linked to ASD in 3-10% of patients (7). An important aspect of genetic testing is that it can offer more information to better differentiate one syndrome from another and prevent any misdiagnosis, as there are many syndromes that present as ASD or with ASD combined with additional symptoms of a genetic condition. Some examples include:

  • Fragile X Syndrome (FXS) commonly coexists with ASD and occurs when there is a change in the gene FMR1 (8). Genetic testing can determine if FMR1 is altered, in which case, a genetic counselor can help individuals and their families to determine their own risk and to understand how to best manage the condition.

  • Williams Syndrome is a rare genetic disorder that presents with behaviors common to those with ASD, so consequently an individual with Williams Syndrome may be diagnosed with ASD if genetic testing is not performed. Other symptoms of Williams Syndrome include high blood pressure, cardiovascular abnormalities, and elevated calcium levels; thus identification of this disorder is necessary for proper care (8). 

  • Angelman Syndrome affects a person’s nervous system and occurs when a section of chromosome 15 is missing (8). Many symptoms of Angelman Syndrome are similar to ASD symptoms, but it is also characterized by an accompanying form of epilepsy. Knowing how to manage seizures and symptoms of epilepsy is critical for the health and safety of those who may experience the condition.

Additionally, people with ASD have an increased likelihood of having anxiety, depression, and ADHD (9). Pharmacogenomics (PGx) is a type of genetic test that reveals differences in genes responsible for making molecules that digest (metabolize) medications. A person’s genes in part determine the likelihood of adverse drug reactions or for a reduced chance of drug effectiveness. PGx is often valuable in flagging medications in certain drug families that an individual may want to avoid.

Patients that have challenges with communicating can benefit significantly by having more information about which medications have the best chances of working. PGx is often included in WES/WGS and proper interpretation of the results communicated to patients and physicians can save patients time, money, and the possibility of unwanted side effects. Genetic counselors are often consulted to interpret these complicated results for both patients and their physicians. Medication groups that can be evaluated by PGx include:

  • Antidepressants

  • Anxiety medications

  • Antibiotics

  • Anesthesias

  • Stimulants

  • Pain medications

  • and others

*Clover Genetics can provide genetic counseling for those with diagnosed or suspected ASD as well as facilitate genetic testing reviewed by both a genetic counselor and a physician. We offer post-test counseling to discuss the results and provide answers to questions, resources, and support for each patient.*

 
 

Is Genetic Testing Controversial?

Although genetic testing provides the benefits of identifying genetic syndromes that may have additional risks or symptoms, like increased risk for cancer or epilepsy, or for aiding in medication selection and management during care for people with ASD, it is still a controversial topic. Some advocates argue that genetic testing may increase discrimination against those who are neurodivergent. In a society that views disabilities through a neurotypical lens, finding a genetic link to ASD may cause people to see ASD as a defect rather than a natural form of neurological diversity (10). Some also fear that testing for ASD will increase abortion rates similar to how abortion rates have increased alongside testing for Down Syndrome (10). There is also concern from many who believe that the money used for genetic testing would be better used for improving the quality of life for individuals with ASD (10).

It is important to note the rational concern many people have regarding the privacy of their genetic data, so it is recommended that any use of technology during diagnostic care should be vetted for security and patients or their caregivers communicate specifically about how or if they want their data stored, archived, or destroyed after testing.

For those who do undergo genetic testing for ASD, they are often met with uncertain results, with only a small number of cases receiving a positive result. Typically, those with a positive result are those with multiple family members with ASD, or those with significant multisystem or more severe diagnoses, including the 30% of ASD patients living with an intellectual disability (7). In this regard, *Clover Genetics Founder and Lead Genetic Counselor, Andy McCarty, MS, LCGC, speaks on the reaction parents often have to results of genetic testing:

“Reactions from parents or the patient can be mixed based on the age of the individualand where they are in their diagnostic journey. Positive results can impact emotions around the loss of the ‘expected child’ if they don’t have testing revleaing a diagnosis  whereas older children and adults often find the positive diagnosis to be a ‘good’ thing as it allows them affirmation of their experiences along with access to services. For the parents, it is common for them to feel relief that it is ‘not their fault’ and a reduction in feelings of shame or guilt based emotions. 

“Negative results often fall into two categories: relief of having ruled something out, or frustration that it did not provide an answer. For patients who receive results that include Variants of Unknown Significance (VUS), many fall into the relief category, but some may have anxiety related to the lack of clarity. Overall, reactions to a VUS versus a negative result are similar but differ based on the lived experiences of each person or family.”

While DNA sequencing has already demonstrated its capacity to change the world, it is vital that the scientific community keep in mind the goals and desires of those living with the condition before moving forward with genetic technology as an avenue for treating or curing a disorder. Some conditions and natural human variation need to be better understood rather than “cured” or changed. The idea of gene editing as a possible cure has been met by some members of the ASD community as appalling or considered eugenics. Many are firm that being Autistic or neurodivergent doesn’t mean a cure is required and that having ASD is not an impairment that needs fixing. Family members and caregivers of ASD patients who cannot advocate for themselves also may feel the opposite and are hopeful for a treatment, not to change who that person is, but rather to relieve stress and discomfort for patients with high-needs. Genetic counselors are there to bridge the gap for all patients and families to help them answer any questions and to fully understand their options without any pressure, judgment, or an agenda beyond supporting individuals and providing information and resources to further their health autonomy.

*Clover Genetics can provide genetic counseling for those with diagnosed or suspected ASD as well as facilitate genetic testing reviewed by both a genetic counselor and a physician. We offer post-test counseling to discuss the results and provide answers to questions, resources, and support for each patient.

Read Part One: Autism Spectrum Disorder

 
 

Citations

1. CDC. “Signs & Symptoms | Autism Spectrum Disorder (ASD) | NCBDDD | CDC.” Centers for Disease Control and Prevention, 28 Mar. 2022, https://www.cdc.gov/autism/signs-symptoms/?CDC_AAref_Val=https://www.cdc.gov/ncbddd/autism/signs.html

2.  “Autism Spectrum Disorder.” National Institute of Mental Health (NIMH), https://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-asd Accessed 16 Aug. 2022. 

3. Nightengale, Laura. “The Autism Spectrum Explained.” OSF HealthCare Blog, 26 June 2019, https://www.osfhealthcare.org/blog/the-autism-spectrum-explained/.

4. Chappell, Bill. “A Nonspeaking Valedictorian with Autism Gives Her College’s Commencement Speech.” NPR, 12 May 2022. NPR, https://www.npr.org/2022/05/12/1098506522/nonspeaking-valedictorian-autism-college-commencement-speech

5. Autism Spectrum Disorder: MedlinePlus Genetics. https://medlineplus.gov/genetics/condition/autism-spectrum-disorder/ Accessed 21 June 2022.

6. William M. Brandler et al. ,Paternally inherited cis-regulatory structural variants are associated with autism. Science360,327-331(2018). https://www.science.org/doi/10.1126/science.aan2261

7. CDC. “Autism Spectrum Disorder, Family Health History, and Genetics” Reviewed May 18, 2022.  https://www.cdc.gov/autism/about/index.html 

8. FirespringInt. “Seven Disorders Closely Related to Autism.” Autism Research Institute, https://www.autism.org/related-disorders/ Accessed 1 Aug. 2022.

9. Autism | NAMI: National Alliance on Mental Illness. https://www.nami.org/Learn-More/Mental-Health-Conditions/Related-Conditions/Autism. Accessed 1 Aug. 2022.

10. BSc, Andréas RB Deolinda, BA. “Is There Genetic Testing For Autism?” Autism Parenting 

Magazine, 29 Sept. 2021, https://www.autismparentingmagazine.com/autism-genetic-testing/ 

11. “Finding Strengths in Autism.” Spectrum | Autism Research News, 12 May 2021, 

https://www.spectrumnews.org/features/deep-dive/finding-strengths-in-autism/

12. “There’s No Autism Epidemic. But There Is an Autism Diagnosis Epidemic.” STAT, 10 Feb. 2022, https://www.statnews.com/2022/02/10/theres-no-autism-epidemic-but-there-is-an-autism-diagnosis-epidemic/.

13. Americans With Disabilities Act of 1990, 42 U.S.C. § 12101 et seq. (1990). https://www.dol.gov/general/topic/disability/ada 

14. Oxford Languages and Google - English | Oxford Languages. https://languages.oup.com/google-dictionary-en/  Accessed 31 July 2022.

15. “LGBTQ Inclusion: Glossary.” UW Medicine, https://www.uwmedicine.org/provider-resource/lgbtq/lgbtq-inclusion-glossary Accessed 31 July 2022.

16. “What You Need to Know About Nonspeaking Autism.” Healthline, 1 Nov. 2021, https://www.healthline.com/health/autism/nonverbal-autism.

17. Nonverbal Autism: Symptoms, Diagnosis, and Treatment. 22 Nov. 2021, https://www.medicalnewstoday.com/articles/non-verbal-autism 

18. Definition of EXOME. https://www.merriam-webster.com/dictionary/exome  Accessed 31 July 2022.

19. Autism Spectrum Disorder (ASD) Screening. MedlinePlus Genetics. https://medlineplus.gov/lab-tests/autism-spectrum-disorder-asd-screening/ Accessed 18 January 2024.