Autism Spectrum Disorder

Trio/Singleton 
Whole Genome Sequencing Test 

Autism Spectrum Disorder (ASD) is a highly heritable neurodevelopmental condition that often affects multiple members within a family (1).

 

Its clinical presentation is variable and frequently accompanied by co-occurring conditions (comorbidities) such as developmental delay, intellectual disability, epilepsy, or ADHD (2).

 

Given this complexity, making a definitive diagnosis using standard assessments alone can be difficult, particularly in younger children (3). However, early identification is essential, as timely intervention has been shown to significantly improve developmental outcomes (4).

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Why Consider Whole Genome Sequencing (WGS)?

 

Complex genetic changes including copy number, exonic, intronic, and splice site variants are known to be associated with ASD and its comorbidities (5).

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WGS offers a comprehensive approach to uncovering the genetic basis of ASD and its comorbidities. It can detect a broad range of variant types in a single test, including:

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• Copy number variants

• Single nucleotide changes and small insertions/deletions

• Intronic and splice site variants

• Mosaic mutations

 

Genetic testing can help reduce the diagnostic odyssey of going from clinician to clinician to define or confirm the diagnosis, which can be costly and emotionally taxing for the family.

 

By identifying pathogenic and likely pathogenic variants, WGS can clarify diagnosis, inform prognosis, guide early management, and reduce the risk of misdiagnosis. ​It is particularly valuable in cases with complex or atypical presentations. Recent studies have demonstrated clinical utilities of genetic diagnoses leading to early patient management changes (6, 7).

 

• Recent consensus guidelines including those from the American College of Medical Genetics and Genomics (ACMG), recommend WGS as a first-line genetic test for children with ASD or unexplained neurodevelopmental disorders (8-12).

 

• WGS is increasingly covered by insurance when medically indicated and ordered by a licensed healthcare provider.​​

a. Understand Other Health Issues (Comorbidities) That Come with Autism, and Management Changes

 

Many children with autism also have other conditions (comorbidities) like delayed speech, learning difficulties, seizures, or ADHD. WGS can help find out if these problems are linked to a specific genetic change.

 

This can give doctors a better idea of what to expect as the child grows, and in some cases, it may lead to specific treatments:

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• Clarify prognosis and likely clinical trajectory

• Inform anticipatory guidance and multidisciplinary care planning

• Guide condition-specific management (e.g., tailored therapies for epilepsy or metabolic disorders)

• Reduce diagnostic delays and unnecessary testing

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b. Determine New (Spontaneous) Genetic Changes

 

Sometimes, autism is caused by a new mutation (de novo variant) that happened in the child and wasn’t inherited from the parents. WGS can detect these.

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c. Help with Family Planning

 

If a child’s autism is caused by a new (de novo) mutation, the chances of it happening again in another child are lower. But if the genetic change is inherited from a parent, the next child could have up to a 50% chance of also being affected.

 

Knowing this helps families plan for future children.

a. Children with ASD and Co-Occurring Conditions (Comorbidities)

 

Genetic testing, particularly Whole Genome Sequencing (WGS), is recommended for children diagnosed with ASD who also present with one or more of the following comorbidities. These additional features increase the likelihood of an underlying genetic etiology.

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• Global developmental delay*

• Speech/language delay*

• Intellectual disability*

• Epilepsy or seizure disorders*

• Motor or movement abnormalities*

• Behavioral disturbances, such as ADHD or aggression

• Dysmorphic features or congenital anomalies*

 

A list of appropriate comorbidities for testing is available upon request.​

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b. Children with Ambiguous or Atypical ASD Presentations

 

Some children may present with complex, overlapping, or unclear clinical features, where the diagnosis of ASD is suspected but not definitive. Examples include:

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• Atypical signs

• Unusual neurological signs not typical of classical ASD*

• Mixed neurodevelopmental and medical phenotypes*

 

In such cases, WGS may uncover genetic explanations and may clarify or even revise the diagnosis, reducing the risk of misdiagnosis and enabling timely intervention and support.

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​*Likely to be insurance-covered indications for testing.

Test Process

 

a. Whole genome sequencing test is performed at Galatea's U.S. CAP-accredited and CLIA-certified clinical laboratory.

 

 

b. Gene Mutation Analysis – ASD and Related Conditions

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Galatea analyzes approximately 415 genes that are closely associated with autism spectrum disorder (ASD) and related comorbidities. These include small-scale genetic changes, such as:

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• Single-letter DNA changes (single nucleotide variants)

• Small insertions/deletions

• Mutations at gene splice sites, which may affect how genes are read by the body

• Copy number variants (CNVs) on all 415 ASD genes and another 40 large chromosomal CNV beyond this list.

 

c. Genome-Wide Analysis Based on Symptoms

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Beyond the 415 core genes, the test also looks at additional genes linked to ASD symptoms and co-occurring issues, based on standardized clinical features (HPO terms), such as:

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• Intellectual disability

• Developmental and language delay

• Neurological or behavioral abnormalities

• Social and communication challenges

 

d. CNV (Copy Number Variant) Analysis

 

The test includes analysis of genes impacted by CNVs, which are larger genetic deletions or duplications. These are often found in children with ASD and are commonly detected using chromosomal microarray in clinical settings.

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However, the Galatea ASD test includes whole genome sequencing (WGS) that can often detect smaller CNVs that are challenging for chromosomal microarray.

 

e. CNV Confirmation with Long-Read Sequencing Technology

 

For ambiguous or complex CNV findings, Galatea may confirm results using long-read sequencing, helping to improve accuracy in challenging patient cases.

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🔹 Positive Finding

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• What it means: A genetic variant was found that is likely to explain the patient's symptoms.

• Also called: Pathogenic or Likely Pathogenic variant.

• Clinical value: May guide diagnosis, treatment, prognosis, or family planning. For example, it could identify a known genetic syndrome linked to ASD or epilepsy.

• Action: Often leads to changes in clinical care (e.g. referrals, monitoring, or therapy adjustments).

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🔹 Negative Finding

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• What it means: No known disease-causing variant was found.

• Caution: This does not mean the child has no genetic condition- just that nothing was found yet using current technology and knowledge.

• Action: Clinical diagnosis still relies on symptoms and assessments. Reanalysis may be useful in the future as new symptoms emerge or as science advances.

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🔹 Uncertain Finding (VUS – Variant of Uncertain Significance)

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• What it means: A genetic change was found, but we don’t yet know if it causes disease.

• Also called: VUS (Variant of Uncertain Significance).

• Action: Often no immediate changes are made to medical care. May be reclassified over time as more evidence becomes available. Family studies or functional data may help clarify it.

Clinical interpretation of results and clinical reports are provided by Galatea’s certified laboratory.

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Physician support is offered in partnership with Nova, which includes:

• Assistance correlating genetic variants with the child’s symptoms

• Help understanding test results and reports

• Support in communicating findings with families

• Next steps for follow-up or genetic counseling

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Genetic Counseling Support is provided by Galatea-affiliated, licensed genetic counselors

 

Insurance Support is available to assist physicians and families with pre-authorization and billing.