{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:51:18Z","timestamp":1787021478827,"version":"build-2736575974"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.14904.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T00:00:00Z","timestamp":1548633600000}}],"reference-count":31,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T00:00:00Z","timestamp":1548633600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["082498"],"award-info":[{"award-number":["082498"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background<\/ns4:bold>\n                    Sex chromosome trisomies (47,XXX, 47,XXY and 47,XYY) are known to be a risk factor for language disorder, but it is hard to predict outcomes, because many cases are identified only when problems are found.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods<\/ns4:bold>\n                    We recruited children aged 5-16 years with all three types of trisomy, and divided them into a High Bias group, identified in the course of investigations for neurodevelopmental problems, and a Low Bias group, identified via prenatal screening or other medical investigations. Children from a twin sample were used to compare pattern and severity of language problems: they were subdivided according to parental concerns about language\/history of speech-language therapy into a No Concerns group (N = 118) and a Language Concerns group (N = 57). Children were assessed on a psychometric battery and a standardized parent checklist. After excluding children with intellectual disability, autism or hearing problems, the sample included 28 XXX, 18 XXY and 14 XYY Low Bias cases and 7 XXX, 13 XXY and 17 XYY High Bias cases.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results<\/ns4:bold>\n                    Variation within each trisomy group was substantial: within the Low Bias group, overall language scores were depressed relative to normative data, but around one third had no evidence of problems. There was no effect of trisomy type, and the test profile was similar to the Language Concerns comparison group. The rate of problems was much greater in the High Bias children with trisomies.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions<\/ns4:bold>\n                    When advising parents after discovery of a trisomy, it is important to emphasise that, though there is an increased risk of language problems, there is a very wide range of outcomes. Severe language problems are more common in those identified via genetic testing for neurodevelopmental problems but these are not characteristic of children identified on prenatal screening.\n                  <\/ns4:p>","DOI":"10.12688\/wellcomeopenres.14904.2","type":"journal-article","created":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T12:05:50Z","timestamp":1548677150000},"page":"143","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Language phenotypes in children with sex chromosome trisomies"],"prefix":"10.12688","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-4033","authenticated-orcid":false,"given":"Dorothy V. M.","family":"Bishop","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7953-8062","authenticated-orcid":false,"given":"Annie","family":"Brookman-Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki","family":"Gratton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4233-8731","authenticated-orcid":false,"given":"Georgina","family":"Holt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5659-9492","authenticated-orcid":false,"given":"Sarah","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Paine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Thornton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9940-6913","authenticated-orcid":false,"given":"Paul 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Neurol."},{"key":"ref-31","article-title":"Woodcock-Johnson III Tests of Cognitive Abilities","author":"R Woodcock","year":"2007"}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-143\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-143\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-143\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,10]],"date-time":"2022-09-10T21:41:34Z","timestamp":1662846094000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-143\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,28]]},"references-count":31,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.14904.2","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.16388.r34707","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.16388.r34701","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.16388.r34705","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.16388.r34701","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.16388.r34705","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.16388.r34707","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,28]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-143\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.16388.r34701, Kate Baker, MRC Cognition and Brain Sciences Unit, and Department of Medical Genetics, University of Cambridge, Cambridge, UK, 29 Jan 2019, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-143\/v2#referee-response-34701","order":0,"name":"referee-response-34701","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.16388.r34707, Laura Zampini, Department of Psychology, University of Milano-Bicocca, Milan, Italy, 14 Feb 2019, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-143\/v2#referee-response-34707","order":1,"name":"referee-response-34707","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Dorothy Bishop<\/b>; <i>Posted: 15 Mar 2019<\/i>; Many thanks to Dr Zampini for her comments on our paper, and for drawing our attention to the study she and colleagues have done, looking at language development in children with trisomy X and Klinefelter's syndrome in children around 24 months of age. Although their sample is small in absolute terms, (7 girls with trisomy X, and 8 boys with Klinefelter syndrome), it is, I believe, unique in having data on a number of these children all studied at the same age, and restricting consideration to cases identified on prenatal screening.&nbsp; Use of a combination of data from parental report and direct observation is a considerable strength of the study, and the follow-up results described in her review above suggest that a parent vocabulary checklist could be very useful in identifying those children with a sex chromosome trisomy who may benefit from early speech-language intervention.&nbsp;I was surprised, though, that our conclusions were thought to be over-optimistic, as my impression was that our results are not so inconsistent with those of Zamipini et al. In both studies, there is a wide range of outcomes, with significant numbers of children having problems, but others within normal limits. Zampini et al report that 60% of their sample had a vocabulary size below the 5 <sup>th<\/sup> percentile at 24 months of age, but 27% scored above the 25 <sup>th<\/sup> percentile. Our concern was that, in reporting our findings, we should not focus only on cases with poor language, but rather that we should indicate the range of outcomes \u2013 which includes some who are relatively unaffected. It is precisely this lack of certainty about the severity of impact that makes it difficult for genetic counsellors to advise parents, but it seems in such a situation the only way forward is to give families information about the full range of possible outcomes, while making them aware that the child is at increased risk of difficulties.&nbsp;I have now added Table 1, showing children's experience of speech-language therapy, as reported by parents, in the Low Risk cases.&nbsp; I have included the cases with autism or intellectual disability, who were more likely to have had had therapy. As with our previous 2011 study, rates of therapy are indeed higher than in a comparison group, but there are still many children who had no contact with speech and language therapy services.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-143\/v2#referee-comment-3822","order":2,"name":"referee-comment-3822","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.16388.r34705, Nancy Raitano Lee, Department of Psychology, Drexel University, Philadelphia, PA, USA, 18 Mar 2019, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-143\/v2#referee-response-34705","order":3,"name":"referee-response-34705","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Dorothy Bishop<\/b>; <i>Posted: 22 Jul 2019<\/i>; We thank Dr Lee for her careful evaluation of our paper.We respond here to the specific questions about maternal age and ethnicity.It is indeed the case that mothers of children in the low bias group were older, as prenatal screening is generally only offered to older mothers.&nbsp;Mother's age at time of child's birth was 37.0 yr (SD = 5.57, N = 56) for the Low Bias group, which included predominantly those identified on prenatal screening, and it was 29.4 yr (SD = 6.18, N = 30) for the High Bias group. These data focus on the children whose data were included in the analyses reported here, i.e. those with language test data and no exclusionary factors. Mother's age was unknown for one child who was adopted.&nbsp; This is a substantial difference, t (54.33) = 5.65, p &lt; .001.&nbsp;However, there was no evidence that mother's age had any impact on the child's language scores, once the bias status was taken into account. On a multiple regression analysis, with general language factor as dependent variable, and bias status and mother's age entered as predictors, the t-test for mother's age was non-significant, t (83) = 0.46, p = .643.&nbsp;Regarding ethnicity, 86% of the low bias group vs 90% of the high bias group were White, and families were included in the study only if English was the main language spoken at home.&nbsp;In general, it is not feasible to equate the High Bias and Low Bias groups for social and environmental factors, but we find it plausible that the difference between these groups is largely due to the way in which they were selected. By definition, children in the High Bias group had the trisomy discovered in the course of investigations for neurodevelopmental problems. We know that most cases of sex chromosome trisomy go undetected: children whose trisomy was not identified prenatally would not be included in the High Bias group if they were problem-free.&nbsp;&nbsp;Regarding speech and language therapy, some data on this were provided in a response we provided to reviewer 2 (please see our response to that review).&nbsp;We don't have plans to analyse the relationships between different aspects of language and cognitive functioning, but the anonymised dataset is available and could be used by other researchers to explore or replicate findings focusing on this aspect.&nbsp;Our thanks again to all reviewers for their constructive comments on our paper. We are glad that this mode of publication allows us to engage with reviewers in this way, and hope that our data will be of use to other researchers in the future.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-143\/v2#referee-comment-3893","order":4,"name":"referee-comment-3893","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was funded by Wellcome Trust Programme Grant 082498. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}