Isolated Nonvisualization of the Fetal Gallbladder Should Be Considered for the Prenatal Diagnosis of Cystic Fibrosis

Abstract

Background: Cystic fibrosis (CF) can be revealed during fetal life by diverse ultrasound digestive abnormalities (USDA) such as fetal echogenic bowel or fetal intestinal loop dilatation, nonvisualization of the fetal gallbladder (NVFGB) being rarely observed in isolation. Only 6 cases of CF revealed by isolated NVFGB have been reported so far in the literature. Furthermore, recent studies suggested that this sign is of poor predictive value for CF. Methods: We report on the results of a 6-year French tricenter study on 1,124 cases of fetal USDA for whom a comprehensive molecular study was performed for CF. Results: Among the 37 CF fetuses, 5 (13.5%) presented with isolated NVFGB at ultrasound (US) examination at 24–31 weeks of gestation. This sign was more frequently observed in CF fetuses than in non-CF fetuses, with a likelihood ratio of 2.7. The genotypes included three c.1521_1523del (F508del) homozygous cases and two compound heterozygous cases for a frequent and a rare CF-causing variant. Discussion: These observations highlight the importance to report on the presence and aspect of the fetal gallbladder at the second trimester US scan and to consider prenatal CFTR molecular analysis in cases of isolated NVFGB.

Molecular Diagnosis and Genetic Counseling of Cystic Fibrosis and Related Disorders: New Challenges

“…Prenatal diagnosis of CF may also be performed in the absence of family history of CF if ultrasound digestive abnormalities such as fetal echogenic bowel, fetal intestinal loop dilatation and non-visualization of the fetal gallbladder are observed during pregnancy [ 28 ]. Depending on national regulations, the term of pregnancy and ultrasound signs, the strategy followed and extent of the study may be the same as for diagnosis.…”

Pregnancy Outcomes of Non-Visualization of The Foetal Gallbladder From A Chinese Tertiary Single Centre And Literature Review

“…In a study conducted by Becdelièvre A, NVFGB + intestinal canal echo enhancement + intestinal canal widening has a high predictive value for the prenatal diagnosis of cystic brosis (likelihood ratio, 31.4) [22] . Bergougnoux et al summarized the prenatal ultrasound features of 37 children with cystic brosis and found that 5 (13.5%) cases only had isolated NVFGB [27] ; CFTR gene testing through invasive prenatal diagnosis is required for the nal diagnosis of cystic brosis. Although the incidence of this disease is low in China, with the increase in global population mobility and the unpredictability of gene mutations, invasive prenatal diagnosis should be considered when NVFGB is observed during pregnancy, especially when it is complicated with other digestive system anomalies.…”

Prenatal Ultrasound Suspicion of Cystic Fibrosis in a Multiethnic Population: Is Extensive CFTR Genotyping Needed?

“…In the cohort of Duguéperoux et al, reporting on 37 fetuses referred for NVFGB, FEB was associated in the five CF-affected fetuses [ 28 ]. However, a recent study including 37 CF fetuses showed isolated NVFGB in five (13.5%) [ 32 ]. Thus, although we did not find any CFTR deleterious variant in our group, CF must be considered in case of NVFGB, isolated or with other digestive signs, and molecular analysis must be proposed to the parents.…”