Research data
My mutation
The family-facing analyzer accepts common IRF2BPL variant formats, maps the result to the protein, shows public ClinVar context when available, and links to a fuller research database for deeper filtering.
Science
IRF2BPL variants cause NEDAMSS (Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, OMIM #618088). This page summarizes what is currently known about the gene, the patient cohort, and the research landscape, based on published literature and reviewed for accuracy as of the date below. Last reviewed: April 2026.
Snapshot counts
- ClinVar IRF2BPL records
- 590
- Curated papers
- 10
- Extracted public observations
- 65
- Protein length
- 796 aa
Literature digest
Latest literature
Iwama et al. 2025 · Primary Cohort
Clinical and genetic spectrum of patients with IRF2BPL syndrome
Iwama et al. 2025 expands the known IRF2BPL syndrome spectrum by describing 10 people from nine families with nine pathogenic variants, eight of them newly reported. The paper is especially useful because it includes missense and in-frame variants, not only truncating variants. Across the cohort, seizures, developmental delay, autism features, dystonia, ataxia, abnormal EEG, and MRI changes appeared in different combinations. For families, the study shows why patient-level detail matters: the same gene can be linked to early epilepsy, later movement symptoms, and variable development.
Read articleChen et al. 2024 · Primary Cohort With Literature Review
Genetic analysis of IRF2BPL in a Taiwanese dystonia cohort: The genotype and phenotype correlation
This 2024 study looked for IRF2BPL changes in 300 unrelated people in Taiwan who had dystonia without a known genetic diagnosis. The researchers found one teenager with a new, disease-causing IRF2BPL variant, p.Gln127Ter, and then compared her features with previously published IRF2BPL cases. The paper shows that IRF2BPL is a rare cause of dystonia, but it also supports an important pattern: where a variant falls in the IRF2BPL protein may influence whether epilepsy, dystonia, ataxia, or regression are more prominent.
Read articleWang et al. 2024 · Primary Case Series With Zebrafish Model
De novo variants of IRF2BPL result in developmental epileptic disorder
This 2024 paper reported three boys with IRF2BPL-related developmental epileptic disorder and tested the gene in a zebrafish model. All three children had developmental delay, infantile epileptic spasms, hypsarrhythmia on EEG, language delay, and developmental regression; two had MRI abnormalities and some movement-related findings. The authors found three de novo IRF2BPL variants and showed that disrupting the zebrafish irf2bpl gene caused shorter body length and seizure-like electrical activity. The study adds clinical details and functional support that IRF2BPL loss can contribute to early epilepsy and developmental regression.
Read articleTreatments and translation
Treatment landscape
April 2026 · Gene therapy update
First-in-human investigational AAV9 gene therapy milestone
In 2025, public updates from Elly's Team and RTW Foundation reported that a first child received an investigational AAV9 gene therapy for IRF2BPL-related NEDAMSS after FDA clearance of an IND for a single-patient treatment. The public materials describe a vector-based approach intended to deliver a functional IRF2BPL coding sequence; this site avoids shorthand that implies the original gene was swapped out, because AAV approaches generally add delivered genetic material rather than editing out the person's original gene. The treatment remains investigational and is not an approved, broadly available therapy.
Ongoing · Natural history and trial readiness
What still needs to be measured
For NEDAMSS, trial readiness is not only about finding more patients. Researchers still need longitudinal data on when regression, seizures, movement symptoms, feeding issues, vision findings, MRI changes, and communication loss appear or progress; variant-level patterns that may affect severity; practical outcome measures that can detect stabilization or slowing; and biospecimens or model systems that connect IRF2BPL variants to mechanism. The completed Cincinnati Children's registry and the GeneReviews summary are useful anchors, but broader treatment planning still depends on continued family and clinician participation.
For research collaboration
If you're a researcher or clinician interested in IRF2BPL — variant data, sample availability, natural-history information, or future trial design — please reach out.