Genetic etiology and phenotypic characteristics of fetuses with 11q deletion syndrome (11q23.3-q25).

Abstract

The 11q deletion (11q-) syndrome is a rare consecutive polygenic deletion disorder. Characterization of the clinical features, genetic etiology and diagnostic strategies associated with 11q deletion syndrome in the prenatal setting is important to understand this syndrome in its entirety. A retrospective review at Longgang District Maternity & Child Healthcare Hospital of Shenzhen City (Shenzhen, China) involving four fetuses diagnosed with 11q- syndrome was conducted to examine the clinical features of this syndrome. The cases were identified through prenatal screening, including maternal serum biochemistry, non-invasive prenatal screening (NIPS), chromosomal microarray analysis (CMA) and karyotyping. Pregnant women with high-risk results from NIPS or prenatal serological screening received early interventional prenatal diagnosis and genetic counseling. Of the two cases that showed a high-risk of 11q- by NIPS, invasive diagnostic procedures confirmed the presence of large terminal deletions on chromosome 11q, encompassing telomeric regions. CMA identified the deletions while karyotyping revealed underlying structural rearrangements, including balanced translocations in both cases. Prenatal ultrasound identified cardiac anomalies, such as ventricular septal defects and truncus arteriosus. The variability and incomplete penetrance of these malformations suggest the influence of polygenic (e.g., modifier genes, genetic background, copy number variations), epigenetic (e.g., DNA methylation, histone modification) and environmental factors (e.g., diet, lifestyle, exposure to toxins). The results demonstrated that the phenotypic expression of 11q- syndrome varies according to the size and gene content of the deleted region. The integration of CMA and karyotyping improves diagnostic accuracy and elucidates the origin of chromosomal alterations. In the single case present in the current study that involved a parental chromosomal translocation, karyotyping was essential for determining the risk of recurrence. These findings contribute to a more precise understanding of genotype-phenotype associations and support the provision of informed prenatal counseling and the clinical management of 11q- syndrome.