Novel pathogenic variants in FOXP3 in fetuses with echogenic bowel and skin desquamation identified by ultrasound

Am J Med Genet A. 2017 May;173(5):1219-1225. doi: 10.1002/ajmg.a.38144. Epub 2017 Mar 20.

Abstract

Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare, X-linked recessive disease that affects regulatory T cells (Tregs) resulting in diarrhea, enteropathy, eczema, and insulin-dependent diabetes mellitus. IPEX syndrome is caused by pathogenic alterations in FOXP3 located at Xp11.23. FOXP3 encodes a transcription factor that interacts with several partners, including NFAT and NF-κB, and is necessary for the proper cellular differentiation of Tregs. Although variable, the vast majority of IPEX syndrome patients have onset of disease during infancy with severe enteropathy. Only five families with prenatal presentation of IPEX syndrome have been reported. Here, we present two additional prenatal onset cases with novel inherited frameshift pathogenic variants in FOXP3 that generate premature stop codons. Ultrasound findings in the first patient identified echogenic bowel, echogenic debris, scalp edema, and hydrops. In the second patient, ultrasound findings included polyhydramnios with echogenic debris, prominent fluid-filled loops of bowel, and echogenic bowel. These cases further broaden the phenotypic spectrum of IPEX syndrome by describing previously unappreciated prenatal ultrasound findings associated with the disease.

Keywords: FOXP3; IPEX; X-linked; prenatal.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Cell Differentiation / genetics*
  • Diabetes Mellitus, Type 1 / congenital*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diarrhea / diagnosis*
  • Diarrhea / genetics*
  • Diarrhea / physiopathology
  • Female
  • Fetus
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / immunology
  • Frameshift Mutation
  • Genetic Diseases, X-Linked / diagnosis*
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / physiopathology
  • Humans
  • Immune System Diseases / congenital*
  • Immune System Diseases / diagnosis
  • Immune System Diseases / genetics
  • Immune System Diseases / physiopathology
  • Male
  • NF-kappa B / genetics
  • NFATC Transcription Factors / genetics
  • Pregnancy
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • Ultrasonography, Prenatal

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • NF-kappa B
  • NFATC Transcription Factors

Supplementary concepts

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