Psychiatric/Behavioral
for neurodevelopmental disorders in consanguineous populations and autism spectrum disorder with exome sequencing
System Profile
Yield Comparison
Clinical Dimensions
- Behavior regression
- Impulsivity
- Severe irritability
- Social withdrawal
- Stereotypies
- Self-injury with DD
- 22q11.2 deletion
- Fragile X
- Prader-Willi
- Smith-Magenis
- Other syndromic psychiatric disorders
- Flat or inappropriate affect
- Stereotyped movements
- Self-injury
- Agitation
- Poor social reciprocity
- Compulsive behaviors beyond developmental level
- Severe anxiety
- Mood swings
- Aggression
- Self-injury
- Tantrums beyond age
- Obsessive behaviors
- Social withdrawal
- Hallucinations with syndromic features
- Abnormal thyroid
- B12 deficiency
- Metabolic derangements (acidosis, hyperammonemia)
- Copper abnormalities
- Methylation study changes in imprinting disorders
- MRI with cortical malformations
- White matter dysmyelination
- Ventriculomegaly
- Structural abnormalities seen in known syndromes (e.g., 22q11.2)
- Neurocognitive testing with global deficits and maladaptive behavior
- Behavioral scales showing syndromic patterns (e.g., PWS, SMS)
- Use of multiple psychotropics at young age
- Requiring antipsychotics, mood stabilizers, or combination therapy with limited psychosocial triggers
- Paradoxical behavior or extreme agitation with low-dose psychotropics
- Sedation far beyond expected
- Unusual EPS sensitivity
- Surgeries for self-injury sequelae, such as repeated wound repairs
- Occasionally ECT hardware in extreme psychiatric disease
- Behavior therapy (CBT, DBT, ABA-like approaches)
- Crisis planning
- Social skills training in the context of known syndromes
- Safety equipment for self-harm prevention
- Sensory integration devices (weighted blankets, etc.)
- Child psychiatry plus neurology and developmental pediatrics
- Complex behavioral phenotypes
- Psych recommending genetic evaluation for syndromic traits
- Bipolar disorder
- Schizophrenia
- Severe anxiety
- Mood disorders with cognitive issues
- Psychosis in adolescence
- Syndromic psych disorders in relatives
- Psychiatric symptoms not attributable solely to trauma or family dysfunction
- Multiple family members with similar issues
- Stable home but severe symptoms
- Irritability
- Abnormal sleep-wake cycle
- Poor state regulation
- Excessive crying without clear cause
- Behavior inconsistent with typical newborns
Red Flag Combinations
Clinical patterns that should prompt consideration of genetic testing
Psychosis + CHD/facial anomalies (22q11.2)
Severe behavior + sleep disruption (Smith-Magenis)
Mood disorder + developmental delay
Anxiety + congenital anomalies
Screening Decision Pathway
When to consider genetic testing for psychiatric/behavioral presentations
graph TD
START["Patient Presents with\nPsychiatric/Behavioral Concerns"] --> SCREEN{"Screen for\nRed Flags"}
SCREEN --> RF1["Abnormal Pediatric Symptom Checklist"]
SCREEN --> RF2["High Vanderbilt scores plus dysmorphism or global ..."]
SCREEN --> RF3["CBCL patterns suggesting syndromic behavior"]
RF1 --> EVAL{"Multiple\nFlags Present?"}
RF2 --> EVAL{"Multiple\nFlags Present?"}
RF3 --> EVAL{"Multiple\nFlags Present?"}
EVAL -->|Yes| TEST["Order Genetic Testing\n(ES/GS)"]
EVAL -->|No| MONITOR["Continue Monitoring\nRe-evaluate if New Findings"]
TEST --> DX["Molecular Diagnosis\n9-57% yield"]
style TEST fill:#dcfce7,stroke:#16a34a,color:#14532d
style DX fill:#bbf7d0,stroke:#16a34a,color:#14532d
style MONITOR fill:#fef3c7,stroke:#d97706,color:#92400e
Screening Red Flags
Findings on routine screening that may indicate genetic etiology
- Abnormal Pediatric Symptom Checklist
- High Vanderbilt scores plus dysmorphism or global delays
- CBCL patterns suggesting syndromic behavior
Exome / Genome Sequencing Indications
Clinical scenarios supporting ES/GS as a diagnostic approach
- Psychiatric illness with developmental delay, congenital anomalies, epilepsy, or strong family clustering
- Syndromic behavioral phenotypes without molecular diagnosis
Key Evidence
Published studies supporting genetic testing for psychiatric/behavioral conditions
| Study | Year | Type | Sample | Yield | Key Finding |
|---|---|---|---|---|---|
| Clinical exome sequencing for genetic identification of rare... | 2014 | Cohort | 814 | 26% | Clinical exome sequencing yielded 26% overall molecular diagnosis in 814 consecu... |
| Exome sequencing in 152 consanguineous families with neurode... | 2017 | Cohort | 152 | 36.8% | 36.8% diagnostic yield in consanguineous NDD families by ES; identified 30 novel... |
| Semiautomated WES workflow for neurodevelopmental disorders | 2019 | Cohort | 106 | 41% | 41% diagnostic yield for duo/quad/trio and 28% for singleton WES in NDD cohort u... |
| Clinical Sequencing Yield in Epilepsy, Autism Spectrum Disor... | 2021 | Meta-Analysis | 32331 | 23.7% | Meta-analysis of 103 studies/32,331 individuals: overall 23.7% yield; epilepsy 2... |
| Proband-only exome sequencing in 403 Indian children with ne... | 2023 | Cohort | 403 | 31.5% | 31.5% diagnostic yield with proband-only ES in large Indian NDD cohort; consangu... |
| Systematic evaluation of genome sequencing for the diagnosti... | 2023 | Cohort | 1612 | 7.8% | Genome sequencing yielded 7.8% diagnostic rate in 1612 ASD quartets and 46.1% in... |
| Comparison of Three Bioinformatics Tools in the Detection of... | 2023 | Cohort | None | 20.5% | 20.5% diagnostic rate in trio-based WES of 220 ASD probands; de novo variants in... |
| The Utility of Exome Sequencing in Diagnosing Pediatric Neur... | 2024 | Cohort | None | 57% | 57% diagnostic yield with WES in 405 children with NDD from consanguineous famil... |
Updated: 2026-02-25
Curated by: human
Status: human reviewed