Novel pathogenic variants in FOXP3 in fetuses with echogenic bowel and skin desquamation identified by ultrasound.
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.
Greenwood Genetic Center, Greenwood, South Carolina.
Raymond J
http://orcid.org/0000-0002-6788-1151
RJ
Louie
Duke University School of Medicine, Durham, North Carolina.
Queenie K-G
QK
Tan
Duke University School of Medicine, Durham, North Carolina.
Jennifer B
JB
Gilner
Greenwood Genetic Center, Greenwood, South Carolina.
R Curtis
RC
Rogers
Duke University School of Medicine, Durham, North Carolina.
Noelle
N
Younge
Duke University School of Medicine, Durham, North Carolina.
Stephanie B
SB
Wechsler
Duke University School of Medicine, Durham, North Carolina.
Marie T
MT
McDonald
Greenwood Genetic Center, Greenwood, South Carolina.
Barbara
B
Gordon
Clemson University, Clemson, South Carolina.
Christopher A
CA
Saski
Greenwood Genetic Center, Greenwood, South Carolina.
Julie R
JR
Jones
University Medical Group, Anderson, South Carolina.
Shelley J
SJ
Chapman
Greenwood Genetic Center, Greenwood, South Carolina.
Roger E
RE
Stevenson
Duke University School of Medicine, Durham, North Carolina.
John W
JW
Sleasman
Greenwood Genetic Center, Greenwood, South Carolina.
Michael J
MJ
Friez
D000328:Adult; D002454:Cell Differentiation / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D003967:Diarrhea / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005333:Fetus; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000276:immunology; D016368:Frameshift Mutation; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007154:Immune System Diseases / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics; D050778:NFATC Transcription Factors / Q000235:genetics; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D016216:Ultrasonography, Prenatal
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016328:NF-kappa B; D050778:NFATC Transcription Factors
FOXP3; IPEX; X-linked; prenatal