TRPM3-Associated Disorders: Clinical Spectrum and Treatment Options
Bibliographic record
Abstract
Background/Purpose: Monoallelic variants in the transient receptor potential melastatin-related type 3 gene (TRPM3) have been associated with neurodevelopmental delay and epilepsy, including epileptic encephalopathy in small case series. However, an in-depth characterization of the broad phenotype spectrum and treatment options is currently lacking. Methods: We performed an international, multicenter, retrospective study including all patients with pathogenic or likely pathogenic TRPM3 variants. Patients were acquired from GeneMatcher and collaborations ( n = 21), and through a systematic literature search following the PRISMA guidelines ( n = 22). Results: We report on 43 individuals with variants in the TRPM3 gene, most frequently the gain-of-function variant p.Val1002Met ( n = 24). Patients presented with developmental delay and/or intellectual disability (93%), global or axial hypotonia (77%), ocular involvement (70%), musculoskeletal anomalies (65%), and dysmorphic features (58%). We highlight the high frequency of epilepsy in 72% of patients. All patients with epilepsy had a developmental and epileptic encephalopathy with or without spike wave activation in sleep (DEE or DEE-SWAS). The most effective anti-seizure medication (ASM) was the TRPM3 channel blocker primidone, with patients showing an improvement in seizure frequency, motor, and speech development. Conclusion: Here, we report the biggest cohort of patients with variants in the TRPM3 gene. Most patients present with developmental delay/intellectual disability and epilepsy. We recommend screening with awake and sleep electroencephalogram to detect DEE (SWAS) and offer early interventions. The TRPM3 channel blocker primidone has shown promising effects and should be considered in every child with a TRPM3 gain-of-function variant.[ 1 ] Publication History Article published online: 26 September 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".