TY - JOUR
T1 - Monochorionic twins with 15q26.3 duplication presenting with selective intrauterine growth restriction and discordant cardiac anomalies
T2 - A case report
AU - Kannan, Suraj
AU - Bodurtha, Joann N.
AU - Hamosh, Ada
AU - Jordan, Christopher
N1 - Funding Information:
This study makes use of data generated by the DECIPHER community. A full list of centres who contributed to the generation of the data is available from https://deciphergenomics.org/about/stats and via email from contact@deciphergenomics.org. Funding for the DECIPHER project was provided by Wellcome.
Funding Information:
S.K. is supported by an NIH Medical Scientist Training Grant. This funding source had no input in the design, collection of data, analysis, interpretation, or writing of this case report
Publisher Copyright:
© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
PY - 2022/8
Y1 - 2022/8
N2 - Background: Duplication of the distal end of chromosome 15q has been previously implicated in a characteristic overgrowth syndrome. Additionally, many patients have other congenital malformations, including cardiac, renal, genital, and musculoskeletal anomalies. However, some patients may present with intrauterine growth restriction and short stature. Different breakpoints within 15q, as well as different environmental factors, may underlie these varied presentations. Case Presentation: We discuss monochorionic-diamniotic twins with a ~345 kb maternally inherited duplication in 15q26.3. The twins presented with discordant pathology—one twin with a single umbilical artery, selective intrauterine growth restriction, and multiple cardiac defects including aortic coarctation, aortic valve stenosis, and ventricular septal defect, whereas the other twin was unaffected. To our knowledge, this case represents the smallest reported duplication of distal 15q. Conclusion: The discordant phenotype seen in the twins is likely due to a complex interplay between genetic and environmental causes. The affected infant presented prenatally with growth restriction and a single umbilical artery rather than overgrowth, potentially due to a unique breakpoint within 15q. This, in turn, may have produced hemodynamic perturbations between the twins, leading to discordant cardiac disease. Our report thus highlights the importance of genetic and nongenetic mechanisms underlying discordant anomalies in monochorionic twins.
AB - Background: Duplication of the distal end of chromosome 15q has been previously implicated in a characteristic overgrowth syndrome. Additionally, many patients have other congenital malformations, including cardiac, renal, genital, and musculoskeletal anomalies. However, some patients may present with intrauterine growth restriction and short stature. Different breakpoints within 15q, as well as different environmental factors, may underlie these varied presentations. Case Presentation: We discuss monochorionic-diamniotic twins with a ~345 kb maternally inherited duplication in 15q26.3. The twins presented with discordant pathology—one twin with a single umbilical artery, selective intrauterine growth restriction, and multiple cardiac defects including aortic coarctation, aortic valve stenosis, and ventricular septal defect, whereas the other twin was unaffected. To our knowledge, this case represents the smallest reported duplication of distal 15q. Conclusion: The discordant phenotype seen in the twins is likely due to a complex interplay between genetic and environmental causes. The affected infant presented prenatally with growth restriction and a single umbilical artery rather than overgrowth, potentially due to a unique breakpoint within 15q. This, in turn, may have produced hemodynamic perturbations between the twins, leading to discordant cardiac disease. Our report thus highlights the importance of genetic and nongenetic mechanisms underlying discordant anomalies in monochorionic twins.
KW - discordant cardiac anomalies
KW - distal 15q duplication
KW - genetic testing
KW - monochorionic-diamniotic twins
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U2 - 10.1002/mgg3.1947
DO - 10.1002/mgg3.1947
M3 - Article
C2 - 35795918
AN - SCOPUS:85133521168
SN - 2324-9269
VL - 10
JO - Molecular Genetics and Genomic Medicine
JF - Molecular Genetics and Genomic Medicine
IS - 8
M1 - e1947
ER -