Fetal Bowel Abnormalities Suspected by Ultrasonography in Microvillus Inclusion Disease: Prevalence and Clinical Significance

Abstract

Microvillus inclusion disease (MVID) is a rare, inherited, congenital, diarrheal disorder that is invariably fatal if left untreated. Within days after birth, MVID presents as a life-threatening emergency characterized by severe dehydration, metabolic acidosis, and weight loss. Diagnosis is cumbersome and can take a long time. Whether MVID could be diagnosed before birth is not known. Anecdotal reports of MVID-associated fetal bowel abnormalities suspected by ultrasonography (that is, dilated bowel loops and polyhydramnios) have been published. These are believed to be rare, but their prevalence in MVID has not been investigated. Here, we have performed a comprehensive retrospective study of 117 published MVID cases spanning three decades. We find that fetal bowel abnormalities in MVID occurred in up to 60% of cases of MVID for which prenatal ultrasonography or pregnancy details were reported. Suspected fetal bowel abnormalities appeared in the third trimester of pregnancy and correlated with postnatal, early-onset diarrhea and case-fatality risk during infancy. Fetal bowel dilation correlated with MYO5B loss-of-function variants. In conclusion, MVID has already started during fetal life in a significant number of cases. Genetic testing for MVID-causing gene variants in cases where fetal bowel abnormalities are suspected by ultrasonography may allow for the prenatal diagnosis of MVID in a significant percentage of cases, enabling optimal preparation for neonatal intensive care.

Sonographic findings of transient marked proximal bowel dilatation in a growth-restricted fetus at 35 weeks’ gestation

“…Clinicians encountering third-trimester fetal bowel dilatation are often confronted with the dilemma of whether or not these sonographic findings are consistent with an acute fetal intra-abdominal event, which may necessitate surgical management in an attempt to preserve potentially compromised fetal bowel, thus indicating the need for immediate delivery at times despite prematurity [1] , [2] , [3] , [4] , [5] . In contrast, nonsurgical conditions including (but not limited to): cystic fibrosis-associated meconium ileus, congenital chloride diarrhea, microvillus inclusion disease, intestinal neuronal dysplasia, and meconium plug syndrome are well established and do not merit immediate surgical intervention [6] , [7] , [8] , [9] , [10] , [11] . Prenatal ultrasound findings of transient dilatation of loops of fetal bowel such as our case, have been reported infrequently [ 16 , 17 ].…”

“…The differential diagnosis of etiologies underlying the relatively infrequent third-trimester sonographic depiction of dilated fetal bowel includes (functional or mechanical) bowel obstruction, intestinal atresia, volvulus, annular pancreas, intestinal malrotation, intussusception, gastrointestinal duplications, cystic fibrosis-associated meconium ileus, congenital chloride diarrhea, microvillus inclusion disease, intestinal neuronal dysplasia, and meconium plug syndrome [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] . Fetal bowel obstruction may be associated with aneuploidy (mostly Trisomy 21 in association with esophageal or duodenal atresia), and rarely select microduplications or deletions, with a detection rate in cases of low risk of aneuploidy of 3.85% by copy number variation sequencing (CNV-seq) in contrast to 7.69% by whole exome sequencing (WES) [12] , [13] , [14] , [15] .…”