Intellectual Disability and Austism
In 1987 President Ronald Reagan proclaimed March as Intellectual Disability Awareness Month as a way to increase public awareness of intellectual disabilities. Intellectual Disability (ID) is a group of genetically heterogeneous disorders characterized by substantial impairment in cognitive abilities, communication, self-direction, and social and behavioral adaptive skills (American Association of Intellectual and Developmental Disabilities, AAIDD). Intelligence is assessed across three domains designated as conceptual, social, and practical ability (Diagnostic and Statistical Manual of Mental Disorder (DSM-5)). ID is not a single entity, but rather a general symptom of neurologic dysfunction. An estimated seven to eight million people have an intellectual disability within the US (Intellectual Disability).
April was declared Autism Awareness Month in 1970 to educate the country about autism and promote inclusion. Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by varying degrees of social impairment, communication ability, and propensity for repetitive behavior(s) and restricted interests (Levy et al. 2009). Although distinct from ID, ASD is often comorbid with ID and other conditions, such as epilepsy, language deficits, and gastrointestinal problems (Sztainberg and Zoghbi. 2016).
Inheritance of ASD is multifactorial—both genetic and environmental factors are involved. While some genetic variants give individuals a high risk of developing ASD, others may not be fully causative on their own. Instead, they may act as risk factors or have variable penetrance. Symptoms may also differ between affected individuals, even within the same family (Hoang et al. 2017). Genetics and environment also influence the development of ID; however, most severe cases of ID have a genetic basis, with some estimates reaching as high as 50-60% (McLaren and Bryson. 1987; Kaufman et al. 2010).
Overall, more males than females are affected by ASD and ID. ASD with or without ID has a male-to-female ratio of about 4:1 (CDC 2014; Christensen et al. 2016). Although about 30% more males are diagnosed with ID than females, the male-to-female ratio decreases as IQ decreases (American Psychiatric Association 2000). Even for X-linked ID, in which most affected individuals are male, females may display symptoms due to skewed X-inactivation (Plenge et al. 2002; Fieremans et al. 2016).
As ASD and ID are often comorbid, PreventionGenetics offers the Autism Spectrum Disorders and Intellectual Disability (ASD-ID) Comprehensive Sequencing Panel. This large panel consists of 2,066 genes that have been shown to have at least a potential association with ASD-ID phenotypes.
As with all exome-based tests, copy number variant (CNV) analysis is offered with the ASD-ID panel. CNV detection via exome sequencing is equally or more sensitive than chromosomal microarray (CMA). This newer option provides the opportunity to bypass standard CMA testing (Reddy et al. 2012; Sahoo et al. 2016). CNV detection and FMR1 CGG-repeat expansion testing together have a diagnostic yield of 11-15% (Schaefer and Mendelsohn. 2013). FMR1 CGG-Repeat Expansion testing is available at PreventionGenetics.
Trio-based studies have reported molecular diagnostic rates as high as 30-40% for developmental phenotypes (Lee et al. 2014; Wright et al. 2015). Therefore, the Family-Trio option is recommended for the highest diagnostic rate. In situations where a trio is not feasible, PreventionGenetics offers additional testing options such as Family – Duo, Patient Only, or Patient Plus. Patient Plus involves sequencing and copy number variant (CNV) analysis of the patient, and then use of the parental specimens to perform targeted testing for the key sequence variants found in the patient.
The ASD-ID panel is the most comprehensive test related to autism and intellectual disability offered by PreventionGenetics. Smaller panels, more specific to the individual disorders are also available, including the Autism Spectrum Disorders Sequencing Panel (108 genes), X-Linked Intellectual Disability Sequencing Panel (128 genes), and Non-syndromic Intellecutal Disability Sequencing Panel (110 genes). Each of these panels also has the option to reflex to any other exome-based tests for a reduced cost, including the ASD-ID panel.
Intellectual Disability. (2017, June 16). Retrieved March 12, 2019, from https://www.parentcenterhub.org/intellectual/
Levy et al. 2009. PubMed ID: 19819542
Sztainberg and Zoghbi. 2016. PubMed ID: 27786181
Hoang et al. 2017. PubMed ID: 28803755
McLaren and Bryson. 1987. PubMed ID: 3322329
Kaufman et al. 2010. PubMed ID: 21124998
Center for Disease Control and Prevention 2014. Morbidity and Mortality Weekly Report 63:1-21. PubMed ID: 24670961
Christensen et al. 2016. PubMed ID: 27031587
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 2000. Text Revision. 4.
Plenge et al. 2002. PubMed ID: 12068376
Fieremans et al. 2016. PubMed ID: 27159028
Schaefer and Mendelsohn. 2013. PubMed ID: 23519317
Reddy et al. 2012. PubMed ID: 22467168
Sahoo et al. 2016. PubMed ID: 27337029
Lee et al. 2014. PubMed ID: 25326637
Wright et al. 2015. PubMed ID: 25529582
Mehregan et al. 2016. PubMed ID: 27179170