| Phenotype | Gene(s) | Study (year) | Sample size | Key stats | Notes/limitations | URL | Evidence IDs |
|---|---|---|---:|---|---|---|---|
| Ovarioleukodystrophy / vanishing white matter disease (aggregate review) | EIF2B1-5, with EIF2B4 and EIF2B5 frequently implicated by missense variants | Escobar-Pacheco et al. (2024) | 20 cases worldwide compiled from 14 reports | Median age at onset 19 years (range 0.6-40); ovarian manifestations: premature ovarian failure 60%, primary amenorrhea 15%, secondary amenorrhea 15%, ovarian dysgenesis 5%; neurologic findings included pyramidal/gait disturbance 45%, epilepsy ~30-35%; frontal horn cystic degeneration on MRI in 45% | Ultra-rare phenotype; statistics are aggregate across all EIF2B genes, not EIF2B4-only; small case numbers limit genotype-specific inference | https://doi.org/10.7759/cureus.64497 | (pqac-00000017, pqac-00000018, pqac-00000019, pqac-00000022) |
| Ovarioleukodystrophy case with explicit EIF2B4 variant | EIF2B4 | Escobar-Pacheco et al. (2024) | 1 new case within the above review | Homozygous EIF2B4 c.725C>T (p.Pro242Leu) identified by NGS; supports causal association of EIF2B4 with ovarioleukodystrophy/VWM spectrum | Single case; useful for gene-specific confirmation but not for prevalence estimation | https://doi.org/10.7759/cureus.64497 | (pqac-00000018) |
| Pediatric genetic white matter disorders cohort | EIF2B3, EIF2B4, EIF2B5 among other genes | Dong et al. (2023) | 13 total patients | EIF2B4 represented in 2 patients; EIF2B3 n=2, EIF2B4 n=2, EIF2B5 n=2; EIF2B4 splice-site variant c.885+2T>G reported as novel; EIF2B-related cases showed bilateral white matter hyperintensities and cystic degeneration noted for EIF2B4/EIF2B5 carriers in the paper summary | Small single-center pediatric cohort; not specific to one phenotype and not designed for prevalence estimates | https://doi.org/10.1186/s13052-023-01555-z | (pqac-00000023) |
| EIF2B4 disease-target association: leukoencephalopathy with vanishing white matter | EIF2B4 | Open Targets platform (accessed in current evidence context) | Association evidence size = 5 | Disease association reported for leukoencephalopathy with vanishing white matter, leukoencephalopathy with vanishing white matter 1, leukoencephalopathy with vanishing white matter 4, and CACH syndrome; highest listed aggregate score in returned set was 0.8301 for "leukoencephalopathy with vanishing white matter" | Platform-level association evidence, not a clinical cohort; evidence size/score are database metrics rather than patient counts | https://platform.opentargets.org | (pqac-00000000) |
| EIF2B4 disease-target association: ovarioleukodystrophy | EIF2B4 | Open Targets platform (accessed in current evidence context) | Association evidence size = 5 | Association reported for ovarioleukodystrophy with score 0.6093 in returned results | Database evidence complements literature but does not provide phenotype frequency or natural-history statistics | https://platform.opentargets.org | (pqac-00000000) |


*Table: This table summarizes recent clinical and database evidence linking EIF2B4 to vanishing white matter disease and ovarioleukodystrophy, emphasizing available case counts, phenotype frequencies, and key limitations. It is useful for quickly separating aggregate EIF2B-family statistics from the more limited gene-specific evidence for EIF2B4.*