The spectrum of brain malformations and disruptions in twins

Published on Sep 1, 2021in American Journal of Medical Genetics Part A
· DOI :10.1002/AJMG.A.61972
Kaylee B. Park1
Estimated H-index: 1
(UW: University of Washington),
Teresa Chapman13
Estimated H-index: 13
(UW: University of Washington)
+ 15 AuthorsWilliam B. Dobyns114
Estimated H-index: 114
(UMN: University of Minnesota)
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.
OBJECTIVE: To compare the short chorionicity of pregnancy. DESIGN: Prospective nationwide population-based EPIPAGE-2 cohort study. SETTING: 546 maternity units in France, between March and December 2011. POPULATION: A total of 1700 twin neonates born between 24 and 34 weeks of gestation. METHODS: The association of chorionicity with outcomes was analysed using multivariate regression models. MAIN OUTCOME MEASURES: First, survival at 2-year corrected age with or without neurosensory impairment, a...
2 CitationsSource
#1Aaron P. Adam (Seattle Children's Research Institute)H-Index: 1
#2Cynthia J. Curry (UCSF: University of California, San Francisco)H-Index: 33
Last. William B. Dobyns (UMN: University of Minnesota)H-Index: 114
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Several recurrent malformation associations affecting the development of the embryo have been described in which a genetic etiology has not been found, including LBWC, MURCS, OAVS, OEIS, POC, VACTERL, referred to here as "recurrent constellations of embryonic malformations" (RCEM). All are characterized by an excess of reported monozygotic discordant twins and lack of familial recurrence. We performed a comprehensive review of published twin data across all six phenotypes to allow a more robust ...
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#2Waleed BrinjikjiH-Index: 58
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#1Ashley L. Lennox (Duke University)H-Index: 9
#2Mariah L. Hoye (Duke University)H-Index: 6
Last. Elliott H. Sherr (UCSF: University of California, San Francisco)H-Index: 55
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#1Renske OegemaH-Index: 10
#2A. James Barkovich (EUR: Erasmus University Rotterdam)H-Index: 2
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#1Kimberly A. Aldinger (Seattle Children's Research Institute)H-Index: 26
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Last. William B. Dobyns (Seattle Children's Research Institute)H-Index: 114
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Cerebellar malformations are diverse congenital anomalies frequently associated with developmental disability. Although genetic and prenatal non-genetic causes have been described, no systematic analysis has been performed. Here, we present a large-exome sequencing study of Dandy-Walker malformation (DWM) and cerebellar hypoplasia (CBLH). We performed exome sequencing in 282 individuals from 100 families with DWM or CBLH, and we established a molecular diagnosis in 36 of 100 families, with a sig...
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#1John M. OpitzH-Index: 111
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Hereditary hemorrhagic telangiectasia (HHT) is generally considered a disorder of endothelial dysfunction, characterized by the development of multiple systemic arteriovenous malformations (AVMs), including within the brain. However, there have recently been a number of reports correlating HHT with malformations of cortical development, of which polymicrogyria is the most common type. Here we present 7 new cases demonstrating polymicrogyria in HHT, 6 of which demonstrate a brain AVM (bAVM) in cl...
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#1Sara Zagaglia (UCL: University College London)H-Index: 7
#2Christina Selch (Marche Polytechnic University)H-Index: 2
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#1Mara Cavallin (Paris V: Paris Descartes University)H-Index: 8
#2Manuele Mine (French Institute of Health and Medical Research)H-Index: 7
Last. Nadia Bahi-BuissonH-Index: 51
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