Prenatal diagnosis of rearrangements in the fetal 22q11.2 region

Abstract

Background: 22q11.2 deletion syndrome (22q11.2DS) and 22q11.2 duplication syndrome (22q11.2DupS) are the most common copy number variations in humans. The clinical phenotypes of these two syndromes are variable, and there are no large sample data on the prenatal detection rate for these two syndromes in the Chinese population. Results: We recruited 411 pregnant women who showed either abnormal prenatal ultrasound findings or positive prenatal BoBs™ results or who had given birth to a child with chromosomal abnormalities. SNP-array analysis and interphase FISH analysis identified five fetuses with 22q11.2 copy number variants (CNVs), three of which were 22q11.2 deletion syndrome (22q11.2DS) (3/411) and two of which were 22q11.2 duplication syndrome (22q11.2DupS). In all 5 cases of diagnosed 22q11.2 abnormalities, inheritance could not be identified because the parents did not undergo further testing. Conclusion: Our case reports provide a detection rate of 22q11.2 CNVs for fetuses with prenatal diagnostic indications, and early diagnosis of these two syndromes was essential for prenatal intervention in these cases. SNP-array technology is an effective tool in the prenatal diagnosis of 22q11.2 CNVs. The prenatal diagnosis of these two syndromes is helpful for early intervention, which is of great clinical significance.

Consequences of 22q11.2 Microdeletion on the Genome, Individual and Population Levels

“…The first PGD by FISH for 22q11.2DS was reported almost twenty years ago, but currently it is very rarely used [ 92 ]. Prenatal diagnosis is available by non-invasive methods: foetal ultrasonography and echocardiography, and invasive methods: chorionic villus sampling (CVS) or amniocentesis followed by FISH (fluorescent in situ hybridization), GCH or SNP-array [ 4 , 93 ]. It is possible to evaluate fetal cells collected through amniocentesis, typically performed at 15–18 weeks gestation, or through CVS at approximately 10–12 weeks gestation.…”

Prenatal diagnosis and genetic study of 22q11.2 microduplication in Chinese fetuses: A series of 31 cases and literature review

“…Beyond the frequently observed ultrasound features of 22q11.2 microduplications (CHD and increased NT), incidences of specific abnormalities vary across studies (Li et al, 2019(Li et al, , 2020Wentzel et al, 2008;Xue et al, 2021). For example, in our study, we documented renal abnormalities (Cases 3, 21, and 27 showed bilateral renal pelvis, multicystic dysplastic kidney, and mild separation of the right renal collecting system, respectively) in three fetuses (9.7%), which exceeds previously reported incidences (3.8%, 2/52).…”

“…The PubMed database search for English articles reporting prenatal cases with 22q11.2 microduplication revealed four articles that included 52 clinical cases (Li et al, 2019(Li et al, , 2020Wentzel et al, 2008;Xue et al, 2021). Among fetuses considered, 20 (38.5%, 20/52) showed no ultrasound abnormalities, while 32 (61.5%, 32/52) exhibited various ultrasound abnormalities in a variety of organ systems.…”

“…Currently, prenatal diagnostic cohort studies related to 22q11.2 microduplication are relatively rare. This is due to the uncertain nature of fetal development and the high variability of disease phenotypes, making 22q11.2 microduplication variants easily overlooked during prenatal diagnosis, thereby limiting the early assessment and clinical management of potential issues (Li et al, 2019(Li et al, , 2020Wentzel et al, 2008;Xue et al, 2021).…”

Occam's razor dulled: the occurrence of multiple genetic diagnoses

“…Patients with a 22q11.2 duplication should be monitored for heart defects, palate abnormalities, feeding difficulties, neutropenia, hypocalcemia, changes in thyroid function, and hearing loss. Patients also have a high risk of developmental and cognitive delays which require early identification and therapy [22].…”