Prenatally diagnosed distal 16p11.2 microdeletion with a novel association with congenital diaphragmatic hernia: a case report

Congenital diaphragmatic hernia (CDH) is a fetal abnormality affecting diaphragm and lung development, which causes a herniation of abdominal organs into the thorax. It is a life‐threatening severe condition affecting ~ one of 3000 newborns with a survival rate of ~67% 1. Approximately 50–80% of CDHs are diagnosed in the prenatal period through ultrasonographic findings of abdominal organs in the thorax, shift of the heart on the right and shift of mediastinum. Cystic adenomatoid malformation of the lung, pulmonary sequestration, bronchogenic cysts, and pulmonary hypoplasia/agenesia needs to be considered in differential diagnosis. Congenital diaphragmatic hernia may occur as an isolated defect, but ~40% of CDH cases are nonisolated and have at least one additional anomaly, such as intrauterine growth retardation (IUGR) and/or other malformations 2. CDH is etiologically heterogeneous; however, more than 50 different genetic causes have been associated with CDH. Chromosome aneuploidies, large chromosome deletions/duplications, and complex chromosome rearrangements identifiable by karyotype are present in 10–35% of CDH cases and occur at greatest frequency in nonisolated, prenatally diagnosed cases 3. An additional 3.5–13% of cases without identifiable karyotype abnormalities have copy number variations (CNVs) detectable by chromosome microarray analysis 4. A CNV associated with CDH maps to 16p11.2 (from ~29.5 Mb to ~30.1 Mb [hg18]), spans approximately 600 kb and causes the proximal 16p11.2 microdeletion syndrome, characterized by developmental delay, autism spectrum disorder, epilepsy, and obesity 5. This deletion is functionally different from the more distal 16p11.2 220 kb‐microdeletion, which may cause developmental delay, behavioral problems, and mild facial dysmorphisms 6. We here report a case of isolated CDH in a fetus at 18 gestational weeks carrying the distal 16p11.2 microdeletion, diagnosed by high‐resolution Comparative Genomic Hybridization array (a‐CGH).