Autism spectrum disorder (ASD) and intellectual disability (ID) have long been considered clinically distinct conditions, but a closer look suggests the two may be linked and share an underlying genetic cause.
First, it is common for ASD and ID to be present in the same patient:
- As many as 85% of patients with a diagnosis of ASD, also have some degree of ID.
- About 40% of patients with ID have features of ASD (Gillberg, 2000).
In fact, ASD and ID share similar features with other neurodevelopmental disorders, such as attention deficit/hyperactivity disorder (ADHD), epilepsy, schizophrenia, and bipolar disorder.
Second, it is common for ID and ASD to cluster within the same family. In fact, epidemiological studies have shown that co-occurrence of neurodevelopmental and psychiatric disorders within a family is the rule, rather than the exception (Finucane & Myers, 2016).
Clinical Diagnoses and Overlapping Definitions
ASD and ID are “artificial” clinical diagnostic distinctions that serve to label behavioral patterns, development, and other findings and symptoms. They are descriptive terms that are useful for many purposes, including school placement and educational planning, therapy, support services, consideration for treatment, and determining insurance coverage for testing.
A clinical diagnosis of ASD or ID relies on a developmental assessment, including observation of behavior, by a trained health professional, usually a behavioral or developmental pediatrician or a neuropsychologist. There is no single laboratory test.
Clinicians and researchers use the Diagnostic and Statistical Manual of Mental Disorder (DSM) to diagnose and classify developmental brain disorders. The American Psychiatric Association (APA) published DSM-5 in 2013, and the definitions share many elements, which are emphasized below.
The DSM-5 defines ASD as a single umbrella disorder characterized by the following:
- Persistent deficits in social communication and social interaction;
- Restricted repetitive patterns of behavior, interests, or activities;
- Symptoms are present in the early developmental period;
- Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning.
The DSM-5 defines ID as:
- The presence of significant limitations in intellectual functioning (e.g., reasoning, learning, and problem solving);
- This domain includes skills in language, reading, writing, math, reasoning, knowledge, and memory.
- Significant limitations in adaptive behavior (i.e., conceptual, social, and practical skills in everyday life);
- This domain includes empathy, social judgment, interpersonal communication skills, the ability to make and retain friendships.
- Onset in childhood (before the age of 18 years).
Molecular Diagnoses and Genetic Testing
A molecular diagnosis of ASD or ID is established through genetic testing, which may identify the specific underlying cause for an individual’s neurodevelopmental symptoms.
There are many rare genetic variants that cause ASD. However, as a group, disease causing genetic variants are the most significant known cause of ASD (De Rubeis & Buxbaum, 2015).
Genetic causes are also often identified in ID, especially when the degree of intellectual disability is significant or severe and when additional medical findings, such as congenital anomalies, are present.
The American College of Medical Genetics, the National Society of Genetic Counselors, and the American Academy of Pediatrics, recommend genetic testing for children diagnosed with ASD and/or ID. Fragile X testing, chromosomal microarray analysis, and next generation sequencing (either an ASD/ID sequencing panel or whole exome sequencing) are being ordered as a standard part of the laboratory investigation for neurodevelopmental disorders. (Schaefer & Mendelsohn, 2013). Large sequencing studies have identified a disease causing variant in about 26–29% of individuals with neurodevelopmental disorders, including 8–20 % of those with ASD (Retter et al., 2015).
The Importance of Family History
When ASD, ID, and other neurodevelopmental and psychiatric diagnoses are present among members of the same family, they should be viewed as potentially having the same cause.
Genetic variants that cause ASD and ID can be inherited from family members who have no, or minimal, manifestations of the condition, and/or express the variant differently. In fact, a family member with the same variant may have different or more severe symptoms or an alternate clinical diagnosis.
Gathering more information about family members who share a genetic variant believed to cause ASD and/or ID can help identify a molecular diagnosis. In some instances, genetic variants are found in a gene whose role in disease has not been clearly established. Testing more than one ‘affected’ family member may yield invaluable information about the significance of such a result. In addition, better understanding the inheritance pattern for a particular condition may help identify other ‘at risk’ relatives.
Why does this matter?
Our understanding of the causes, inheritance, and variable symptoms and signs of neurodevelopmental and psychiatric disorders is evolving, and much is to be learned. As additional genetic causes are identified, and as our understanding of how known causes can manifest variably among individuals increases, it will be possible to make earlier molecular diagnoses. This will ultimately improve medical management, enable earlier intervention, and potentially identify effective treatments.
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De Rubeis S, Buxbaum JD. Genetics and genomics of autism spectrum disorder: embracing complexity. Hum Mol Genet. 2015;24:R24–31.
Gillberg C, Billstedt E. Autism and Asperger coexist with other clinical disorders. Acta Psychiatr Scand. 2000;102:321-330.
Retterer K, Juusola J, Cho MT, Vitakaza P, Millan F, Gibellini F, et al. Clinical application of whole-exome sequencing across clinical indications. Genetics in Medicine. 2016;18:696-704.
Schaefer GB, Mendelsohn NJ, Professional Practice and Guidelines Committee. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 Guideline Revisions. Genet Med. 2013;15:399–407.