Risk and Clinical Significance of Idiopathic Preterm Birth in Microvillus Inclusion Disease

Abstract

Microvillus inclusion disease (MVID) is a rare enteropathy caused by mutations in the MYO5B or STX3 gene. MVID is a disease that is difficult to manage with clinical heterogeneity. Therefore, knowledge about factors influencing MVID morbidity and mortality is urgently needed. Triggered by a recent study that reported a high percentage of preterm births in twelve cases of MVID, we have conducted a comprehensive retrospective study involving 88 cases of MVID with reported gestational ages. We found that moderate to late preterm birth occurred in more than half of all cases, and this was particularly prominent in MYO5B-associated MVID. Preterm birth in MVID counterintuitively correlated with higher birth weight percentiles, and correlated with higher stool outputs and a significantly shorter average survival time. Data from this study thus demonstrate an increased risk of preterm birth in MYO5B-associated MVID, with a clinical impact on morbidity and mortality. Adverse effects associated with preterm birth should be taken into account in the care of children diagnosed with MVID. Documentation of gestational age may contribute to a better prognostic risk assessment in MVID.

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

“…The presence of prenatal bowel abnormalities suspected by ultrasonography in cases of MVID did not correlate with preterm birth or birthweight. This is in agreement with the notion that preterm birth and birthweight in MVID appeared to be associated with MYO5B mutations, rather than with bowel dysfunctions as such [ 6 ], whereas our results suggest that the occurrence of suspected fetal bowel abnormalities in MVID was directly related to bowel disease rather than to variants in specific MVID-associated genes (i.e., MYO5B, STX3, or STXBP2 ). This is in agreement with the notion that these three genes cooperate in the same cellular pathway that controls electrolyte exchange at the brush border of intestinal epithelial cells [ 29 , 38 ].…”

“…MVID is associated with high risk of preterm birth and lower birthweight [ 6 , 35 ]. Polyhydramnios has also been associated with a higher risk of preterm birth [ 36 ].…”

“…(Prenatal) lifetime prevalence was calculated over the period of 1978–2022 by dividing the number of reported MVID cases with suspected prenatal bowel abnormalities by the total number of MVID cases for which the presence or absence of suspected prenatal bowel abnormalities was reported or, alternatively, by the total number of MVID cases reported. Other statistical analyses were essentially performed as described earlier [ 6 ]. Odds ratios (OR) were calculated as measures of association.…”

“…Only supportive treatment is available, involving life-long maintenance of hydration, electrolytes, and nutrition with total parenteral nutrition [ 5 ]. Many MVID patients who were reported to have died did not survive the neonatal period or infancy [ 6 ], but other MVID patients have reached childhood or adolescence [ 7 , 8 , 9 , 10 ]. Although the reason for this heterogeneity in disease progression among patients is not known, adequate neonatal intensive care of MVID patients is expected to improve chances of survival.…”

“…The SLC26A3 - and SLC9A3 -encoded proteins—the chloride-bicarbonate exchanger and the sodium-hydrogen exchanger protein-3 protein, respectively—are targets of the MYO5B -encoded myosin Vb protein and are affected in the intestinal epithelium in MVID [ 16 , 17 ]. Accordingly, some MVID patients show fecal chloride and/or sodium concentrations as high as those in CCD and CSD patients [ 6 ]. Furthermore, morphological defects of the fetal intestine have been observed in a mouse model of MVID [ 18 ].…”