Prenatal diagnosis of a pure 15q distal trisomy derived from a maternal pericentric inversion: A case report

Abstract

Distal trisomy or duplication of 15q is a very rare chromosomal disorder; most of the previously reported cases were derived from unbalanced translocations involving chromosome 15 and another chromosome, whereas other mechanisms (e.g. duplication) have rarely been reported. We herein report a very rare prenatal case of a partial 15q trisomy, a 42.64-Mb duplication of 15q22.2-q26.3, arising from a maternal pericentric inversion of chromosome 15 (p11q22) that was not the result of an unbalanced translocation or duplication, and was not associated with concomitant partial monosomy. Fetal ultrasound revealed isolated thickened nuchal translucency at 12 weeks and multiple abnormalities in the second trimester, including early growth restriction, unilateral ventriculomegaly, narrow cavum septi pellucidi with hypoplasia of the corpus callosum, unilateral postaxial polydactyly, clenched hands and clubfoot with clawing of the toes, and a particular general dysplastic and hypotrophic aspect of the heart. The distinctive aspects of the present case may help to refine the phenotype associated with distal duplication 15q. To the best of our knowledge, this is the first report of a prenatal diagnosis with a 15q22.2-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component.

Mosaic embryo transfer—first report of a live born with nonmosaic partial aneuploidy and uniparental disomy 15

“…The presence of 3 copies of the 15q11.2q12 region encompassing the imprinted SNRPN locus, when the additional copy is of maternal origin, is associated with intellectual disability, ataxia, seizures, and behavioral problems ( 11 ). Overlapping duplications of the distal 15q23q26.3 region have been reported with neurodevelopmental phenotypes and variable congenital abnormalities, including overgrowth, renal anomalies, and dysmorphic features ( 12 , 13 , 14 , 15 ). In addition, the large isodisomic region at 15q14-q22 may potentially be clinically relevant.…”

Monochorionic twins with 15q26.3 duplication presenting with selective intrauterine growth restriction and discordant cardiac anomalies: A case report

“…It should be noted that several case reports of a distal 15q26.3 duplication‐related overgrowth presentation have been described that do not involve IGF1R , suggesting that other genes in this region may also play a role in the syndromic features (De Schepper et al, 2017 ; Leffler et al, 2016 ). Moreover, others have described patients with 15q26.3 duplication involving IGF1R presenting with IUGR, failure to thrive, and short stature rather than overgrowth (Burada et al, 2021 ; Cannarella et al, 2017 ; Roggenbuck et al, 2004 ). This is particularly relevant to our case study.…”

“…Congenital cardiac anomalies have been previously identified in approximately 50% of patients with distal 15q duplications (Cannarella et al, 2017 ). These have included a range of pathologies, including patent ductus arteriosus, mitral valve stenosis, septal defect, atrioventricular canal, aortic coarctation, hypoplastic left heart, Ebstein anomaly, and others (Burada et al, 2021 ; Cannarella et al, 2017 ; Thorsson et al, 2013 ). Interestingly, Thorsson et al identified a primary critical region in 15q26.3 that appears to be involved in cardiac pathogenesis (Thorsson et al, 2013 ).…”

“…In addition to overgrowth, patients may present with other congenital malformations, including craniosynostosis, cardiac and renal malformation, genital anomalies, and limb abnormalities (Cannarella et al, 2017 ). Patients with distal 15q duplications have also presented with intrauterine growth restriction (IUGR) and short stature rather than the classic overgrowth (Burada et al, 2021 ; Roggenbuck et al, 2004 ). These variable presentations may be due to different breakpoints within 15q, leading to differential regulation of IGF1R .…”