Clinically Significant Genetic Results in Fetuses With Isolated Horseshoe Kidney

Area of Science:

• Medical Genetics
• Prenatal Diagnosis
• Urology

Background:

• Isolated horseshoe kidney (HSK) is a congenital anomaly with potential genetic underpinnings.
• Prenatal diagnosis of isolated HSK necessitates further investigation into underlying genetic causes.

Purpose of the Study:

• To evaluate the diagnostic yield of genetic testing in fetuses diagnosed with isolated horseshoe kidney (HSK).

Main Methods:

• Retrospective analysis of 95 cases with isolated fetal HSK diagnosed via second-trimester ultrasound.
• Invasive prenatal diagnosis using chromosomal microarray analysis (CMA) for copy number variant (CNV) detection.
• Trio exome sequencing (ES) offered for cases with negative CNV results.

Main Results:

• Chromosomal microarray analysis (CMA) detected pathogenic CNVs in 3.2% of cases (1 isochromosome X, 1 duplication 16p13.11, 1 deletion 7q11.22).
• Trio exome sequencing (ES) in 45 cases identified disease-causing variants in PSMD12 and KMT2D, yielding a 4.4% diagnostic rate for monogenic conditions.
• Combined genetic testing yielded a significant diagnostic rate for underlying genetic abnormalities.

Conclusions:

• Genetic investigation, including CMA and ES, offers a valuable diagnostic yield in fetuses with isolated HSK.
• The findings support the recommendation for genetic testing in pregnancies complicated by isolated fetal HSK.
• Identifying genetic causes can inform genetic counseling and management strategies.