Table 3.

Genetic etiologies and additional associated findings in fetuses with double bubble sign

Prenatal finding / suspected diagnosis	Cases, n	Prenatal polyhydramnios, n	Postnatal surgical findings	Genetic testing results
Trisomy 21a	6	4	3 duodenal atresia	6 trisomy 21 karyotype
			1 duodenal atresia/duodenal web
Isolated	7	6	5 duodenal atresia	6 normal microarray
			2 duodenal atresia/annular pancreas	1 microdeletionb
Heterotaxyc	3	2	2 duodenal atresia/annular pancreas	1 heterotaxy-associated ZIC3 gene variant
			1 duodenal atresia/duodenal web + gastric volvulus	1 normal microarray with negative ZIC3/CFC1 gene testing
				1 normal karyotype and microarray
Cardiac defect	2	2	2 duodenal atresia	1 normal microarray and karyotype
				1 normal cfDNA screen with no further genetic testing
Bilateral renal agenesisd	1	0	N/A	N/A
Vertebral anomaly	1	1	duodenal atresia	normal karyotype, microarray, and whole-exome sequencing
Echogenic bowel	1	1	duodenal atresia	normal microarray

^aTrisomy 21: 6 total cases – 4 diagnosed by prenatal chromosomal analysis, 2 suspected prenatally by cfDNA screen result and ultrasound findings, both confirmed by postnatal karyotype.

^bInterstitial microdeletion of chromosome band 4q22.3.

^cHeterotaxy cases included multiple anomalies including complex cardiac defects and right-sided stomachs.

^dDelivered at outside hospital with neonatal demise, lost to follow-up postnatally.