RESUMO
BACKGROUND: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a monogenic disorder characterized by early onset fatal multi-system autoimmunity due to loss-of-function mutations in the gene encoding the forkhead box P3 (FOXP3) transcription factor which is crucial for the development, maturation, and maintenance of CD4+ regulatory T (T-reg) cells. Various autoimmune phenomena such as enteropathy, endocrinopathies, cytopenias, renal disease, and skin manifestations are characteristic findings in patients affected by IPEX syndrome. OBJECTIVES: In this systematic review, we focus on both clinical and demographic characteristics of IPEX patients, highlighting possible genotype-phenotype correlations and address prognostic factors for disease outcome. METHODS: We performed a literature search to systematically investigate the case reports of IPEX which were published before August 7th, 2017. RESULTS: A total of 75 articles (195 patients) were identified. All IPEX patients included had FOXP3 mutations which were most frequently located in the forkhead domain (nâ¯=â¯68, 34.9%) followed by the leucine-zipper domain (nâ¯=â¯30, 15.4%) and repressor domain (nâ¯=â¯36, 18.4%). Clinical manifestations were as follows: enteropathy (nâ¯=â¯191, 97.9%), skin manifestations (nâ¯=â¯121, 62.1%), endocrinopathy (nâ¯=â¯104, 53.3%), hematologic abnormalities (nâ¯=â¯75, 38.5%), infections (nâ¯=â¯78, 40.0%), other immune-related complications (nâ¯=â¯43, 22.1%), and renal involvement (nâ¯=â¯32, 16.4%). Enteropathic presentations (Pâ¯=â¯0.017), eczema (Pâ¯=â¯0.030), autoimmune hemolytic anemia (Pâ¯=â¯0.022) and food allergy (Pâ¯=â¯0.009) were associated with better survival, while thrombocytopenia (Pâ¯=â¯0.034), septic shock (Pâ¯=â¯0.045) and mutations affecting the repressor domain (Pâ¯=â¯0.021), intron 7 (Pâ¯=â¯0.033) or poly A sequence (Pâ¯=â¯0.025) were associated with increased risk of death. Immunosuppressive therapy alone was significantly associated with increased cumulative survival compared to patients who received no treatment (Pâ¯=â¯0.041). CONCLUSIONS: We report the most comprehensive summary of demographic and clinical profiles derived from a total of 195 IPEX patients with deleterious mutations in FOXP3. Analysis of our findings provides new insights into genotype/phenotype correlations, and clinical and genetic factors associated with increased risk of death and response to treatment strategies.