The goal of the TRPM3Care-registry is to record the disease progression of patients with TRPM3-associated disorders. This allows us to compare the disease progression and the success of different therapies, as well as to examine their impact on quality of life.

Transient Receptor Potential Melastatin 3 (TRPM3) is a calcium-permeable, non-selective cation channel that is widely expressed in the central and peripheral nervous system, sensory neurons, pancreatic β-cells, vascular smooth muscle, and several other tissues. TRPM3 plays an essential role in intracellular calcium signaling and contributes to neuronal excitability, thermosensation, nociception, insulin secretion, and cellular homeostasis.

Over the past decade, pathogenic germline variants in TRPM3 have been identified as the cause of a rare neurodevelopmental disorder characterized by developmental delay, intellectual disability, epilepsy, hypotonia, movement disorders, and variable neurobehavioral manifestations. The clinical spectrum is expanding as additional patients are identified through next-generation sequencing, revealing considerable phenotypic variability and an incomplete understanding of genotype-phenotype relationships.

Due to the rarity of TRPM3-associated disorders, clinical knowledge is currently limited to relatively small case series and individual case reports. Consequently, there is an urgent need for systematic collection of standardized clinical, genetic, imaging, electrophysiological, and longitudinal outcome data to better characterize the natural history of these disorders and to facilitate future therapeutic research.

Purpose of the Registry

The TRPM3Care Registry is an international, multicenter observational registry established to collect comprehensive clinical and molecular data from individuals carrying pathogenic or likely pathogenic variants in the TRPM3 gene, as well as individuals with variants of uncertain significance when supported by compatible clinical findings.

The registry aims to provide a centralized resource for clinicians and researchers to improve understanding of disease mechanisms, define the phenotypic spectrum, establish genotype-phenotype correlations, identify prognostic markers, evaluate disease progression, and support the development of evidence-based clinical management recommendations.

Inclusion Criteria:

• Variant in the TRPM3 gene

Exclusion Criteria:

• no consent from patient/familiy

All patients with TRPM3 variants can be included