Prenatal ultrasound phenotypic and genetic etiology of the 17q12 microduplication syndrome

Abstract

BackgroundSeveral studies have reported on the clinical phenotype of the 17q12 microduplication syndrome, a rare autosomal dominant genetic disorder, in children and adults, but few have reported on its prenatal diagnosis. This study analyzed the prenatal ultrasound phenotypes of the 17q12 microduplication syndrome to improve the understanding, diagnosis, and monitoring of this disease in fetuses.MethodsA retrospective analysis of 8,200 pregnant women who had received an invasive antenatal diagnosis at tertiary referral hospitals between January 2016 and August 2021 was performed. Amniotic fluid or cord blood was sampled from the pregnant women for karyotyping and chromosome microarray analysis (CMA).ResultsThe CMA revealed microduplication in the 17q12 region of the genome in five fetuses, involving fragments of about 1.5–1.9 Mb. Five fetuses with the 17q12 microduplication syndrome had different prenatal ultrasound phenotypes, including duodenal obstruction (two fetuses); mild ventriculomegaly, dysplasia of the septum pellucidum, agenesis of the corpus callosum (one fetus); and a strong echo in the left ventricle only (one fetus). The ultrasound phenotype of one fetus was normal. Among the five fetuses with the 17q12 microduplication syndrome, the parents of three refused CNV segregation analysis, while CNV segregation analysis was performed for the remaining two fetuses to confirm whether the disorder was inherited maternally or paternally, with normal phenotypes. After genetic counseling, the parents of those two fetuses chose to terminate the pregnancy, while the parents of the three unverified fetuses continued the pregnancy, with normal follow-up after birth.ConclusionAlthough prenatal ultrasound phenotypes in fetuses with the 17q12 microduplication syndrome are highly variable, our study has highlighted the distinct association between duodenal obstruction and the 17q12 microduplication syndrome. Understanding the relationship between the pathogenesis of the 17q12 microduplication in prenatal ultrasound phenotypes and its long-term prognosis will contribute to better genetic counseling concerning the 17q12 microduplication syndrome, which is still a challenge.

Identification of copy number variations among fetuses with isolated ultrasound soft markers in pregnant women not of advanced maternal age

“…CNVs have been detected in pregnant women with fetal USMs, suggesting that more attention should be paid to CNVs in pregnant women with fetal USMs, especially P CNVs [8, 13,[23][24][25][26]. In our study cohort, CNVs were more common than aneuploidies.…”

Prenatal Genetic Analysis of Kidney Abnormalities

“…The main clinical features of 17q12 microdeletion syndrome are structural or functional abnormalities in the kidney and urethra, type 5 diabetes, and neurodevelopmental or neuropsychiatric disorders. [15] It has been reported that 11 cases of 17q12 microdeletion fetus have enhanced renal echo ultrasound, 2 cases also accompanied by kidney enlargement, [4] 88% of 17q12 microdeletion fetal prenatal ultrasound enhanced renal echo, but no obvious change in kidney size. [7] In our study, 12 cases showed enhanced renal echo among 14 patients with 17q12 microdeletion syndrome, which was consistent with the above report.…”

Prenatal Genetic Analysis of Fetal 17q12 Microdeletion Syndrome and Relation to Kidney Abnormalities

“…The main clinical features of 17q12 microdeletion syndrome are structural or functional abnormalities in the kidney and urethra, type 5 diabetes, and neurodevelopmental or neuropsychiatric disorders. [15] It has been reported that 11 cases of 17q12 microdeletion fetuses have exhibited enhanced renal echo ultrasound, and 2 cases were accompanied with kidney enlargement. [4] In another study, a total of 88% of 17q12 microdeletion fetuses presented with enhanced prenatal ultrasound renal echo, but no obvious changes in kidney size.…”