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Park KB, Chapman T, Aldinger KA, et al. The spectrum of brain malformations and disruptions in twins. Am J Med Genet A. 2020;185(9):2690-2718doi: 10.1002/ajmg.a.61972.
Park, K. B., Chapman, T., Aldinger, K. A., Mirzaa, G. M., Zeiger, J., Beck, A., Glass, I. A., Hevner, R. F., Jansen, A. C., Marshall, D. A., Oegema, R., Parrini, E., Saneto, R. P., Curry, C. J., Hall, J. G., Guerrini, R., Leventer, R. J., & Dobyns, W. B. (2021). The spectrum of brain malformations and disruptions in twins. American journal of medical genetics. Part A, 185(9), 2690-2718. https://doi.org/10.1002/ajmg.a.61972
Park, Kaylee B, et al. "The spectrum of brain malformations and disruptions in twins." American journal of medical genetics. Part A vol. 185,9 (2021): 2690-2718. doi: https://doi.org/10.1002/ajmg.a.61972
Park KB, Chapman T, Aldinger KA, Mirzaa GM, Zeiger J, Beck A, Glass IA, Hevner RF, Jansen AC, Marshall DA, Oegema R, Parrini E, Saneto RP, Curry CJ, Hall JG, Guerrini R, Leventer RJ, Dobyns WB. The spectrum of brain malformations and disruptions in twins. Am J Med Genet A. 2021 Sep;185(9):2690-2718. doi: 10.1002/ajmg.a.61972. Epub 2020 Nov 18. PMID: 33205886; PMCID: PMC8683564.
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Am J Med Genet A. 2021 Sep;185(9):2690-2718. doi: 10.1002/ajmg.a.61972. Epub 2020 Nov 18.

The spectrum of brain malformations and disruptions in twins.

American journal of medical genetics. Part A

Kaylee B Park, Teresa Chapman, Kimberly A Aldinger, Ghayda M Mirzaa, Jordan Zeiger, Anita Beck, Ian A Glass, Robert F Hevner, Anna C Jansen, Desiree A Marshall, Renske Oegema, Elena Parrini, Russell P Saneto, Cynthia J Curry, Judith G Hall, Renzo Guerrini, Richard J Leventer, William B Dobyns

Affiliations

  1. University of Washington School of Medicine, Seattle, Washington, USA.
  2. Department of Radiology, University of Washington School of Medicine, Seattle, Washington, USA.
  3. Seattle Children's Research Institute, Center for Integrative Brain Research, Seattle, Washington, USA.
  4. Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.
  5. Brotman Baty Institute for Precision Medicine, Seattle, Washington, USA.
  6. Department of Pathology, University of California San Diego, La Jolla, California, USA.
  7. Neurogenetics Research Group, Reproduction Genetics and Regenerative Medicine Research Cluster, Vrije Universiteit Brussel, Brussels, Belgium.
  8. Pediatric Neurology Unit, Universitair Ziekenhuis Brussel, Brussels, Belgium.
  9. Department of Anatomic Pathology and Neuropathology, University of Washington School of Medicine, Seattle, Washington, USA.
  10. University Medical Center Utrecht, Department of Genetics, Utrecht, The Netherlands.
  11. Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Meyer Children's Hospital, University of Florence, Florence, Italy.
  12. Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.
  13. Genetic Medicine, Department of Pediatrics, University of California San Francisco, Fresno, California, USA.
  14. Departments of Medical Genetics and Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, Canada.
  15. Department of Neurology, Royal Children's Hospital, Murdoch Children's Research Institute and University of Melbourne Department of Pediatrics, Melbourne, Australia.
  16. Department of Pediatrics, Division of Genetics and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.

PMID: 33205886 PMCID: PMC8683564 DOI: 10.1002/ajmg.a.61972

Abstract

Twins have an increased risk for congenital malformations and disruptions, including defects in brain morphogenesis. We analyzed data on brain imaging, zygosity, sex, and fetal demise in 56 proband twins and 7 less affected co-twins with abnormal brain imaging and compared them to population-based data and to a literature series. We separated our series into malformations of cortical development (MCD, N = 39), cerebellar malformations without MCD (N = 13), and brain disruptions (N = 11). The MCD group included 37/39 (95%) with polymicrogyria (PMG), 8/39 (21%) with pia-ependymal clefts (schizencephaly), and 15/39 (38%) with periventricular nodular heterotopia (PNH) including 2 with PNH but not PMG. Cerebellar malformations were found in 19 individuals including 13 with a cerebellar malformation only and another 6 with cerebellar malformation and MCD. The pattern varied from diffuse cerebellar hypoplasia to classic Dandy-Walker malformation. Brain disruptions were seen in 11 individuals with hydranencephaly, porencephaly, or white matter loss without cysts. Our series included an expected statistically significant excess of monozygotic (MZ) twin pairs (22/41 MZ, 54%) compared to population data (482/1448 MZ, 33.3%; p = .0110), and an unexpected statistically significant excess of dizygotic (DZ) twins (19/41, 46%) compared to the literature cohort (1/46 DZ, 2%; p < .0001. Recurrent association with twin-twin transfusion syndrome, intrauterine growth retardation, and other prenatal factors support disruption of vascular perfusion as the most likely unifying cause.

© 2020 Wiley Periodicals LLC.

Keywords: Dandy-Walker malformation; cerebellar hypoplasia; malformations of cortical development; twinning; twins; zygosity

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