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Type: Journal article
Title: Cerebral palsy: causes, pathways, and the role of genetic variants
Author: MacLennan, A.
Thompson, S.
Gecz, J.
Citation: American Journal of Obstetrics and Gynecology, 2015; 213(6):779-788
Publisher: Elsevier
Issue Date: 2015
ISSN: 0002-9378
Statement of
Alastair H. MacLennan, Suzanna C. Thompson, Jozef Gecz
Abstract: Cerebral palsy (CP) is heterogeneous with different clinical types, comorbidities, brain imaging patterns, causes, and now also heterogeneous underlying genetic variants. Few are solely due to severe hypoxia or ischemia at birth. This common myth has held back research in causation. The cost of litigation has devastating effects on maternity services with unnecessarily high cesarean delivery rates and subsequent maternal morbidity and mortality. CP rates have remained the same for 50 years despite a 6-fold increase in cesarean birth. Epidemiological studies have shown that the origins of most CP are prior to labor. Increased risk is associated with preterm delivery, congenital malformations, intrauterine infection, fetal growth restriction, multiple pregnancy, and placental abnormalities. Hypoxia at birth may be primary or secondary to preexisting pathology and international criteria help to separate the few cases of CP due to acute intrapartum hypoxia. Until recently, 1-2% of CP (mostly familial) had been linked to causative mutations. Recent genetic studies of sporadic CP cases using new-generation exome sequencing show that 14% of cases have likely causative single-gene mutations and up to 31% have clinically relevant copy number variations. The genetic variants are heterogeneous and require function investigations to prove causation. Whole genome sequencing, fine scale copy number variant investigations, and gene expression studies may extend the percentage of cases with a genetic pathway. Clinical risk factors could act as triggers for CP where there is genetic susceptibility. These new findings should refocus research about the causes of these complex and varied neurodevelopmental disorders.
Keywords: causes; cerebral palsy; DNA variants; epidemiological risk factors; genetic variants; genomics; heterogeneity; whole exome sequencing
Description: Letter to the Editor. From the Australian Collaborative Cerebral Palsy Research Group at the Robinson Research Institute, the University of Adelaide, Adelaide, Australia
Rights: Crown Copyright © 2015 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( nd/4.0/).
DOI: 10.1016/j.ajog.2015.05.034
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Paediatrics publications

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