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
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
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Neuropediatrics |
| Vol/bind | 56 |
| Udgave nummer | S 01 |
| Sider (fra-til) | S1-S24 |
| ISSN | 0174-304X |
| DOI | |
| Status | Udgivet - 2025 |