IPEX Syndrome: Genetics and Treatment Options

Genes (Basel). 2021 Feb 24;12(3):323. doi: 10.3390/genes12030323.


(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.

Keywords: FOXP3 mutations; HSCT; IPEX syndrome; autoimmunity; genetic engineering.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allografts
  • Animals
  • Diabetes Mellitus, Type 1 / congenital*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / therapy
  • Diarrhea* / diagnosis
  • Diarrhea* / genetics
  • Diarrhea* / metabolism
  • Diarrhea* / therapy
  • Female
  • Forkhead Transcription Factors* / genetics
  • Forkhead Transcription Factors* / metabolism
  • Genetic Diseases, X-Linked* / diagnosis
  • Genetic Diseases, X-Linked* / genetics
  • Genetic Diseases, X-Linked* / metabolism
  • Genetic Diseases, X-Linked* / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immune System Diseases / congenital*
  • Immune System Diseases / diagnosis
  • Immune System Diseases / genetics
  • Immune System Diseases / metabolism
  • Immune System Diseases / therapy
  • Infant
  • Infant, Newborn
  • Male
  • Mutation*


  • FOXP3 protein, human
  • Forkhead Transcription Factors

Supplementary concepts

  • Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome