Clinical utility of multigene panel testing in adults with epilepsy and intellectual disability
Bibliographic record
Abstract
OBJECTIVE: To determine the diagnostic yield of a commercial epilepsy gene panel in adults with chronic epilepsy and accompanying intellectual disability, given that genetic evaluation is often overlooked in this group of patients. METHODS: This is a cross-sectional study analyzing the results of epilepsy gene panels including up to 185 genes in adult epilepsy patients with intellectual disability, according to Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Patients with acquired structural brain abnormalities or known chromosomal abnormalities were excluded. RESULTS: From approximately 600 patients seen from January 2017 to June 2018 at a single academic epilepsy center, 64 probands and two affected relatives (32 males, mean age = 31 years ± 10) were selected and clinically tested. Fourteen probands (14/64 = 22%; four males, mean age = 32 years ± 10) were found to have pathogenic or likely pathogenic variants in the following genes: SCN1A, GABRB3, UBE3A, KANSL1, SLC2A1, KCNQ2, SLC6A1, HNRNPU, STX1B, SCN2A, PURA, and CHD2. Six variants arose de novo, and the inheritance was not determined in eight. Nine probands (64%) had severe or profound intellectual disability, and five (35%) had autistic features. Eight patients (57%) had a diagnostic change from presumptive clinical diagnosis prior to genetic testing. SIGNIFICANCE: We were able to demonstrate that a commercial epilepsy gene panel can be an important resource in clinical practice, identifying the etiology in 22% of adults with epilepsy and intellectual disability. The diagnostic yield is similar to previously reported pediatric cohorts. Larger samples would be required to evaluate the more prevalent genotypes among adult epilepsy patients.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".