Prenatal Bowel Findings in Male Siblings With a Confirmed FOXP3 Mutation

Abstract

There are multiple etiologies for fetal dilated bowel loops on ultrasonography (US), and we present a unique case of male siblings with a forkhead box P3 (FOXP3) mutation. Both children presented with fetal bowel anomalies on prenatal US. Family histories of cystic fibrosis and immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome were reported. Amniocentesis in both pregnancies identified a normal male karyotype and the familial mutation associated with IPEX syndrome. IPEX syndrome is one of a group of conditions known as congenital diarrhea disorders. Other congenital diarrhea disorder cases have presented with similar prenatal US findings. As a result of these associations, we suggest considering IPEX syndrome as a potential cause of fetal bowel anomalies, particularly with a known family history. However, continued research into the phenotypic and genotypic correlations for IPEX syndrome is likely needed to better understand this possible prenatal presentation.

Scolopendra subspinipes mutilans L. Koch Ameliorates Rheumatic Heart Disease by Affecting Relative Percentages of CD4+CD25+FoxP3 Treg and CD4+IL17 T Cells

“…CD4 + CD25 + Treg cells are generated in the thymus and have been reported to mitigate autoimmune myocarditis [19]. The dysfunction of CD4 + CD25 + Treg cells may lead to RHD occurrence and FoxP3 regulates Treg cell development and function [20, 21]. CD4 + IL-17 T cells have been reported to be associated with bacterial infection and inflammatory responses [22, 23].…”

Intrauterine IPEX

“…Smith et al (17) described a 37-week small-for-gestational age neonate with a new FOXP3 mutation (c.1227_1235delTGAGCTGGA), who developed IDDM on the 2nd day of life, and refractory diarrhea on day 13th, and did not survive. The two siblings described by Griswold et al (16), reported because of their ultrasonographic bowel features, presented IPEX manifestations in the 1st days of life and had a confirmed FOXP3 mutation (c.1150A > G). The family described by Levy-Lahad and Wildin (5) had three siblings with severe intrauterine growth restriction, neonatal IDDM, and enteropathy, none of them surviving.…”

“…Prenatal ultrasonography exploration revealed bowel anomalies in all individuals, except one, whose analyses were described: hyperechoic bowel, prominent fluid-filled loops of bowel, and echogenic debris in the stomach being the most frequent findings (6,7,11,12). Griswold et al (16) observed dilated loops of bowel in two IPEX fetuses from the same family, who had manifestations in the neonatal period. In cases with severe dermatitis, hyperechoic skin with projections was described (7,12).…”

“…It is estimated that 25% of stillbirths are attributable to genetic causes (8,77). Although IPEX is considered as an extremely rare disease, with no well-established frequency in the population, professionals involved in prenatal care must be attentive to its detection, with the most important warning signs being: (i) recurrent male fetal losses, stillbirths, or premature infants in the family history (see references in Table 1); (ii) dilated bowel loops or hyperechogenic bowel on fetal ultrasonography (US), mainly if associated with skin alterations (6,7,10,12,16); and (iii) plurivisceral inflammation with eosinophils found in fetal postmortem pathology (10,11). Diagnostic confirmation is reached by karyotyping and subsequent DNA sequencing, nowadays by whole exome sequencing (WES), being the mutation always confirmed by Sanger DNA sequencing (8,10,47,48).…”

“…Diagnostic confirmation is reached by karyotyping and subsequent DNA sequencing, nowadays by whole exome sequencing (WES), being the mutation always confirmed by Sanger DNA sequencing (8,10,47,48). Regarding bowel abnormalities in fetal US, there are multiple potential etiologies, such as cystic fibrosis, congenital anomalies of gastrointestinal tract, congenital diarrhea disorders, being IPEX an example of the last group (16). Figure 3 depicts a work-flow diagram for the prenatal identification of intrauterineonset IPEX.…”