IPEX Syndrome: Genetics and Treatment Options.

Iwona Ben-Skowronek

doi:10.3390/genes12030323

Abstract

(1) Background: IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome characterizes a complex autoimmune reaction beginning in the perinatal period, caused by a dysfunction of the transcription factor forkhead box P3 (FOXP3). (2) Objectives: Studies have shown the clinical, immunological, and molecular heterogeneity of patients with IPEX syndrome. The symptoms, treatment, and survival were closely connected to the genotype of the IPEX syndrome. Recognition of the kind of mutation is important for the diagnostics of IPEX syndrome in newborns and young infants, as well as in prenatal screening. The method of choice for treatment is hematopoietic stem cell transplantation and immunosuppressive therapy. In children, supportive therapy for refractory diarrhea is very important, as well as replacement therapy of diabetes mellitus type 1 (DMT1) and other endocrinopathies. In the future, genetic engineering methods may be of use in the successful treatment of IPEX syndrome. (3) Conclusions: The genetic defects determine a diagnostic approach and prognosis, making the knowledge of the genetics of IPEX syndrome fundamental to introducing novel treatment methods.

Highlights

Polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome characterizes complex autoimmune reactions beginning in the perinatal period and caused by dysfunction of the transcription factor forkhead box P3 (FOXP3) [1,2,3,4]
FOXP3 plays a key role in controlling the regulatory T cell subset, and its dysfunction leads to autoimmunity [1,2,3,4,5]
Recognition of the kind of mutation is important for the diagnostics of IPEX syndrome in newborns and young infants, as well as in prenatal screening

Summary

Introduction

Polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome characterizes complex autoimmune reactions beginning in the perinatal period and caused by dysfunction of the transcription factor forkhead box P3 (FOXP3) [1,2,3,4]. The FOXP3 gene is located in the centromeric region of X chromosome Xp11.23–Xq13.3 Mutations of this gene cause the deformation and malfunction of protein localized in the DNA-binding domain (forkhead domain). Half of the examined children presented with a FOXP3 mutation, while the rest were diagnosed with an IPEX-like syndrome because of no identifiable FOXP3 mutations Those patients presented an X-like syndrome connected to other phenotype dysregulation genes: STAT5b, STAT1, STAT3, IL2RA, CTLA4, LRBA, TTC7A, TTC37, LRBA, and DOCK8 [6]. An overview of the current knowledge about the pathophysiology, genetics, and therapeutic perspectives is very important for the diagnosis and treatment of patients with IPEX syndrome and for understanding the mechanisms of autoimmunity

Genetics of IPEX Syndrome

Epidemiology

Clinical Features and Their Pathophysiology

Enteropathy

Diagnostic Methods

Treatment for IPEX Syndrome

Findings

Concluding Remarks