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http://crossmark.crossref.org/dialog/?doi=10.1007/s00204-016-1843-3&domain=pdf
Web End = Arch Toxicol (2016) 90:29172929 DOI 10.1007/s00204-016-1843-3
REVIEW ARTICLE
http://crossmark.crossref.org/dialog/?doi=10.1007/s00204-016-1843-3&domain=pdf
Web End = Risk factors for Down syndrome
Fabio Copped1http://orcid.org/0000-0002-3081-6647
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http://orcid.org/0000-0002-3081-6647
Web End = Abstract Down syndrome (DS) originates, in most of the cases (95 %), from a full trisomy of chromosome 21. The remaining cases are due to either mosaicism for chromo-some 21 or the inheritance of a structural rearrangement leading to partial trisomy of the majority of its content. Full trisomy 21 and mosaicism are not inherited, but originate from errors in cell divisions during the development of the egg, sperm or embryo. In addition, full trisomy for chromo-some 21 should be further divided into cases of maternal origin, the majority, and cases of paternal origin, less than 10 %. Among cases of maternal origin, a further stratication should be performed into errors that have occurred or originated during the rst meiotic division in the maternal grandmothers body and errors that occurred later in life during the second maternal meiotic division. This complex scenario suggests that our understanding of the risk factors for trisomy 21 should take into account the above stratication as it reects different individuals and generations in which the rst error has occurred. Unfortunately, most of the available literature is focused on maternal risk factors, and the only certain risk factors for the birth of a child with DS are advanced maternal age at conception and recombination errors, even though the molecular mechanisms leading to chromosome 21 nondisjunction are still a matter of debate. This article critically reviews the hypotheses and the risk factors which have been suggested to contribute to the birth of a child with DS, including folate metabolism, dietary, lifestyle, environmental, occupational, genetic and
* Fabio Copped [email protected]
1 Section of Medical Genetics, Medical Genetics Lab., Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy
Received: 2 August 2016 / Accepted: 29 August 2016 / Published online: 7 September 2016 Springer-Verlag Berlin Heidelberg 2016
epigenetic factors, with focus on maternal and paternal risk factors, and taking into account the possible contribution of the maternal grandmother and that of the developing trisomic embryo, in a complex scenario depicting the...