Autism spectrum disorders (autism spectrum disorder – ASD) are complex neurodevelopmental conditions characterized by challenges or difficulties in social interaction and communication, as well as restricted, repetitive behavior. The diagnostic process for ASD has traditionally focused on behavioral assessments. However, advances in medicine have introduced a range of new, advanced diagnostic tests that help understand the biological underpinnings of ASD.

Importance of genetic testing in ASD

What is whole exome sequencing (WES)?

WES is a genetic test that sequences the protein-coding regions of genes from the genome. These regions, known as exons, are thought to contain approximately 85% of disease-causing mutations.

WES can identify genetic mutations that may contribute to ASD. This test is especially meaningful for families with a history of ASD or related, pervasive developmental disorders. Studies show that WES can identify clinically relevant genetic variants in 25-30% of cases, providing key information for personalized interventions and management.

Most common WES findings

Gen	Type of mutation	Associated feature of ASD
SHANK3	Deletion / Mutation	Social and communication deficits, intellectual disability
FMR1	Expansion of the CGG trinucleotide repeat	Fragile X syndrome often occurs in ASD
CHD8	Mutation	Macrocephaly, unusual facial features, gastrointestinal problems
SYNGAP1	Mutation	Intellectual disability, epilepsy, motor abnormalities
TSC1/TSC2	Mutation	Tuberous sclerosis complex, high prevalence of ASD
PTEN	Mutation	Macrocephaly, developmental delay, Cowden syndrome

If you are considering whole exome sequencing of your child, the Ginekaliks genetic laboratory offers comprehensive testing and expert guidance . Contact us now to learn more about how WES can provide valuable insights into the diagnosis and management of your child's ASD.

Other genetic tests

• Chromosomal microarray (CMA): CMA detects copy number variations (deletions or duplications of DNA segments) that may be associated with ASD.
• Targeted gene panels: These tests look for mutations in specific genes known to be associated with ASD, offering a more focused approach than WES.
  

Gut microbiome analysis

New research suggests that gut health may influence neurological development and behavior, a concept known asstomach-brain axis. Analysis of stool samples can reveal imbalances in the gut microbiota, potentially leading to targeted dietary or probiotic interventions.

The most common dysbiosis

• Reduced diversity: Individuals with ASD may have less diverse gut bacteria, which is critical for overall gut health.
• Altered composition: Specific changes in bacterial species, such as increased Clostridia and decreased Bifidobacteria, have been observed in some individuals with ASD.
  
• Gastrointestinal symptoms: A higher prevalence of gastrointestinal problems, such as constipation, diarrhea, and abdominal pain, has been observed in individuals with ASD, potentially related to microbiome imbalance.
  

electroencephalogram (EEG)

An EEG, which records electrical activity in the brain, can detect epilepsy, which occurs at a higher rate in people with ASD. Quantitative Electroencephalography (QEEG) can assess brain function and the patterns of activity.

Advanced recording techniques

1. Magnetic resonance imaging and functional magnetic resonance imaging (fMRI): These techniques of imaging provide detailed insights into brain structure and function, contributing to a deeper understanding of neural differences in ASD. fMR detects changes in blood flow associated with nerve activity. It is particularly good at understanding brain function and identifying regions involved in specific tasks.

Most common functional magnetic resonance imaging findings

Morphological

• Brain Volume: Early brain overgrowth followed by a plateau is a common finding in young children with ASD.
• Altered connectivity: Differences in the structure of the brain's white matter, which affects how different parts of the brain communicate.
  

Functional

• Neural activity: Atypical patterns of neural activity and connectivity in individuals with ASD, particularly in areas related to social processing and sensory response.
• Resting-state functional magnetic resonance imaging: Differences in default neural network activity, which is critical to understanding the impact of ASD on brain function.
  - Positron emission tomography (PET): It uses a radioactive tracer to visualize areas of metabolic activity and chemical functioning in the brain. It is useful for examining brain metabolism and blood flow.

Most common positron emission tomography findings

• Altered brain metabolism: PET scans can detect variations in glucose metabolism in certain brain regions, indicating altered neuronal activity.
• Neurotransmitter systems: PET allows investigation of neurotransmitter systems, such as serotonin and dopamine pathways, which are often implicated in ASD.
  
• Brain inflammation: Some PET studies suggest the presence of neuroinflammation in certain brain regions in individuals with ASD, potentially contributing to behavioral symptoms.
  
• Implications for diagnosis and treatment: By highlighting specific neurobiological differences, PET scanning may help tailor more effective treatment strategies and potentially aid in early diagnosis.
  

Both PET and fMR have their own unique advantages and applications. While fMR is more commonly used to understand functional changes in the brain, PET scans provide key insights into the brain's metabolic processes. In the context of ASD, both imaging techniques contribute to a more comprehensive understanding of the neurological aspects of the condition.

Additional diagnostic tests

1. Metabolic and biochemical testing: Tests for metabolic disorders that may mimic or contribute to ASD symptoms.
2. Neuropsychological Assessment: Detailed cognitive and behavioral assessments to understand an individual's strengths and challenges.
   
3. Sensory Processing Assessment: Assessment of sensory sensitivities or challenges common in ASD.
   
4. Speech and Language Evaluation: In-depth analysis of communication skills and challenges.
   
5. Emerging Biomarkers: Research is ongoing into potential biomarkers in blood, saliva, or other body fluids that could aid in the diagnosis or understanding of ASD.
   
6. Integration of artificial intelligence and machine learning: New technologies are being explored for their potential to analyze complex data from various tests to aid in diagnosis and personalized treatment planning.
   

The ASD diagnosis landscape extends beyond behavioral assessments to include a variety of advanced diagnostic tests. These tests, especially genetic analyzes such as whole exome sequencing, offer insight into the biological factors that contribute to ASD. Such information can guide personalized treatment and management strategies, marking a significant step forward in the care and understanding of ASD.

Although this article covers the most prominent and advanced diagnostic tests in ASD, it is important to stay abreast of the latest research and developments in the field. The complexity of ASD requires a multifaceted diagnostic approach, combining genetic, neurological, and behavioral assessments to tailor the most effective interventions.

Frequently asked questions

1. How gut microbiome analysis helps in the diagnosis of ASD

• Analysis of the gut microbiome can reveal imbalances that may affect neurological development, offering insights for potential dietary or probiotic interventions.

1. Are there any imaging tests used in the diagnosis of ASD?

• Yes, advanced imaging techniques such as magnetic resonance imaging and functional magnetic resonance imaging are used to understand differences in brain structure and function in individuals with ASD.

1. What is the role of genetic testing in diagnosing ASD?

• Genetic testing, such as whole exome sequencing, helps identify genetic mutations that may contribute to ASD, aiding in personalized treatment approaches.

1. What is whole exome sequencing (WES) and how can it help with ASD?

• Whole exome sequencing is a genetic test that sequences the coding regions of genes in the genome. It can identify genetic mutations that may contribute to ASD, helping to understand your child's specific condition and guide personalized care.

1. What information can WES provide about my child with ASD?

• WES can detect specific genetic mutations associated with ASD, which can help understand the potential cause of the condition, associated risks, and implications for family planning.

1. Is WES recommended for all children with ASD?

• WES is especially helpful if there is a family history of ASD or related disorders (pervasive developmental disorders). It is best to consult a genetic counselor to understand if WES is appropriate for your child.

1. How is WES performed?

• WES involves a simple blood test. The sample is then analyzed in a laboratory to sequence the exons of the genes.

1. Where can I do WES for my child?

• Many genetic laboratories offer WES. We recommend that you consider the Gynecalyx genetic laboratory, known for their expertise in genetic testing and personalized care.

1. What should I do if a genetic mutation is detected?

• It is important to discuss the results with a genetic counselor who can guide you through the implications of the findings and next steps in terms of management and treatment.