Prenatal detection of interstitial 18p11.31‐p11.22 microduplications: Phenotypic diversity and literature review

Abstract

Introduction Pure duplication of chromosome 18p is rare, with clinical phenotypes ranging from normal or slight abnormalities to various degrees of mental retardation. It remains difficult to establish a clear genotype‐phenotype correlation. Methods Chromosomal karyotyping analysis was performed on cultured amniotic fluid cells from three cases. Single nucleotide polymorphism (SNP) array analysis was carried out using the Illumina Human CytoSNP‐12 BeadChip. We also carried out a review of the literature regarding 18p11 microduplication. Results G‐banding analysis showed that the three cases had normal karyotypes. SNP array results showed 0.48‐ to 1.6‐Mb microduplications of 18p11.31‐p11.22 (chr18: 6995739‐8713088) in these cases, encompassing different degrees of LAMA1 duplication. Follow‐up analysis showed that the parents of both cases 1 and 2 chose termination of pregnancy. Case 3 presented with normal growth and physical development. Currently, there is not enough evidence supporting the pathogenicity of LAMA1 triplosensitivity. Conclusion We described three prenatal cases with 18p11.31‐p11.22 microduplications involving part of the LAMA1 locus. There might be phenotypic diversity associated with 18p11.31‐p11.22 microduplications. To avoid unnecessary abortions for pregnancies such as these, comprehensive genetic counseling should be offered.

Clinical utility of chromosomal microarray analysis to detect copy number variants: Experience in a single tertiary hospital

“…For example, the 18p11.31p11.2 duplication detected in asymptomatic patient A2 was classified as VUS, and confirmed as deriving from a healthy father. However, previous studies described that this variation is related to short stature, microcephaly and intellectual delay [15]. Hence, patients and family members should be periodically evaluated through genetic counseling.…”

Shared Neurodevelopmental Perturbations Can Lead to Intellectual Disability in Individuals with Distinct Rare Chromosome Duplications

“…Moreover, the chromosome rearrangements identified in our patients are rare, with few cases reported so far. These duplicated regions have been reported as pathogenic and ID is a recurrent clinical finding in the affected individuals [ 16 , 21 , 26 ]. Therefore, we used network analysis in an attempt to identify the potential sharing of biological processes and genes responsible for the pathophysiology of ID in rare duplications.…”

“…The 8q24.13q24.3 duplication identified is a rare chromosomal rearrangement associated with dysmorphic features, growth delay, and ID [ 13 , 14 , 15 , 16 ]. Moreover, variable levels of ID and cerebellum hypoplasia were described in patients with 18p11 duplications, however, few cases of pure duplications in this region have been reported with similar rearrangements so far [ 17 , 18 , 19 , 20 , 21 ]. Duplication at Xq22.3q27.2 is a condition with region enriched in genes related to neurological function involving many cases of ID, behavioral problems, holoprosencephaly, and cerebellar vermis hypoplasia [ 22 , 23 , 24 , 25 , 26 ].…”

Clinical characterization of chromosome 5q21.1–21.3 microduplication: A case report

“…Currently, chromosomal microarray analysis (CMA) is considered a first-tier diagnostic tool for these children [2]. Through prenatal diagnosis of CMA, some microdeletions or microduplications can be detected before birth to avoid unnecessary abortions or birth defects [3]. The clinical features of some chromosome 5 microduplications have been described previously [4][5][6][7][8].…”