Identification of a novel variant of FOXP3 resulting in severe immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome highlights potential pitfalls of molecular testing

Pediatr Dermatol. 2022 May;39(3):483-485. doi: 10.1111/pde.14936. Epub 2022 Feb 22.

Abstract

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare genetic disorder that typically presents in the first year of life with severe diarrhea, autoimmune endocrine disorder, and inflammatory dermatitis, most commonly an eczematous dermatitis. IPEX syndrome is caused by variants in the FOXP3 gene leading to dysregulation of T-regulatory (Treg) cells and an aberrant immune response. Here, we present a case of severe IPEX syndrome diagnosed following whole genome sequencing (WGS) in a 2-week-old boy with bloody mucoid diarrhea, failure to thrive, and a diffuse eczematous dermatitis. As multiple variants of interest were identified with WGS, this case highlights the importance of relating the clinical symptoms to the genetic results.

Keywords: genetic diseases/mechanisms; genodermatoses; immunodeficiency.

Publication types

  • Case Reports

MeSH terms

  • Diabetes Mellitus, Type 1* / congenital
  • Diarrhea / diagnosis
  • Diarrhea / genetics
  • Eczema*
  • Forkhead Transcription Factors / genetics
  • Genetic Diseases, X-Linked* / diagnosis
  • Genetic Diseases, X-Linked* / genetics
  • Humans
  • Immune System Diseases* / congenital
  • Immune System Diseases* / diagnosis
  • Immune System Diseases* / genetics
  • Intestinal Diseases* / genetics
  • Male
  • Molecular Diagnostic Techniques
  • Mutation
  • Polyendocrinopathies, Autoimmune* / diagnosis
  • Polyendocrinopathies, Autoimmune* / genetics
  • Syndrome

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors

Supplementary concepts

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