Diagnostic Value of Exome Sequencing in Isolated Polyhydramnios
Vered Offen Glassner1, Adi Botvinik1, Adi Mory1
1Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Objective:
To evaluate the diagnostic yield of exome sequencing (ES) in isolated polyhydramnios.
Methods:
This retrospective study included 40 cases of isolated polyhydramnios. All patients underwent screening for gestational diabetes mellitus (GDM) and chromosomal microarray analysis (CMA). ES was performed in CMA-negative cases, along with targeted testing for spinal muscular atrophy, myotonic dystrophy type 1, and Prader-Willi syndrome.
Results:
Pathogenic or likely pathogenic variants were identified in 7 cases, yielding a 17.5% diagnostic rate. Diagnostic yield was 12% (2/17) in mild cases and 22% (5/23) in moderate-severe cases. Diagnoses included Bartter syndrome (KCNJ1, BSND, MAGED2), Noonan syndrome (RIT1), Osteopathia Striata with Cranial Sclerosis (AMER1), and AUTS2-related neurodevelopmental disorder. In addition, one case was diagnosed postnatally with myotonic dystrophy 1. Two ES-positive cases had concurrent GDM. Postnatal follow-up showed normal development in 85% of live-born infants, with a few cases of global or speech delay.
Conclusions:
ES yields a substantial diagnostic benefit in isolated polyhydramnios, including mild cases and those with GDM. These findings support incorporating ES into the diagnostic approach for isolated polyhydramnios.
