An Updated Individual-Patient-Data Systematic Review and Meta-Analysis of Reported DOCK8 Deficiency Cases (2017–2026): Genotype, Phenotype, Malignancy, Infection Spectrum, and Transplant Outcomes

Background: Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal-recessive combined immunodeficiency marked by severe cutaneous viral infections, atopy with elevated IgE, malignancy, and early mortality without hematopoietic stem-cell transplantation (HSCT). Foundational syntheses predate the current transplant era and biologic therapy. Objective: It aims to provide an updated individual-patient-data (IPD) synthesis of DOCK8 deficiency cases reported from 2017 to 2026. Methods: Following PRISMA 2020 and PRISMA-IPD guidance, we searched PubMed/MEDLINE (with full Boolean strings provided for Embase, Scopus, Web of Science and Cochrane CENTRAL) for reports with extractable individual data on confirmed DOCK8 deficiency. Two-stage screening, Murad-2018 risk-of-bias assessment, random-effects Freeman–Tukey pooled proportions (with a random-intercept logistic model as a sensitivity analysis), and reconstructed Kaplan–Meier analyses were performed. Results: Of 360 records, 56 full texts were assessed, and 41 studies were included; 29 provided individual data for 64 patients from 22 countries, and 12 contributed aggregate data. Sixty-three potentially eligible reports were paywalled and could not be retrieved, and non-English reports were excluded, introducing possible retrieval and language bias. Consanguinity was reported in 40/43 (93%); the genotype spectrum was dominated by large deletions and splice/intronic variants. Eczema (72%), cutaneous viral infection (80%) and bacterial infection (64%) predominated. The pooled proportion alive at last reported follow-up was 87.3% (95% CI 81.1–92.6); this is a cross-sectional proportion over variable follow-up and is not a long-term survival estimate, as reconstructed age-specific Kaplan–Meier survival fell to approximately 53% by age 20 (exploratory analysis). Pooled malignancy prevalence was 10.6% (95% CI 3.4–20.7; I2 = 66%), and pooled post-HSCT survival was 86.3% (95% CI 79.0–92.5). Conclusions: Contemporary reports reaffirm the severe infectious and malignant burden of DOCK8 deficiency and support HSCT as definitive therapy, alongside emerging biologic (dupilumab, siltuximab) and gene-directed strategies. Findings are constrained by reporting, retrieval and language bias and by reconstructed IPD; completion of the planned multi-database searches and independent second-reviewer verification are ongoing to finalise the evidence base.