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Etiological diagnosis in limb reduction defects and the number of affected limbs: A population‐based study in the Northern Netherlands

Limb reduction defects (LRDs) that affect multiple limbs are considered to be more often heritable, but only few studies have substantiated this. We aimed to investigate if an etiological diagnosis (genetic disorder or clinically recognizable disorder) is more likely to be made when multiple limbs a...

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Autores principales: Bergman, Jorieke E. H., Löhner, Katharina, van der Sluis, Corry K., Rump, Patrick, de Walle, Hermien E. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756893/
https://www.ncbi.nlm.nih.gov/pubmed/32954639
http://dx.doi.org/10.1002/ajmg.a.61875
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author Bergman, Jorieke E. H.
Löhner, Katharina
van der Sluis, Corry K.
Rump, Patrick
de Walle, Hermien E. K.
author_facet Bergman, Jorieke E. H.
Löhner, Katharina
van der Sluis, Corry K.
Rump, Patrick
de Walle, Hermien E. K.
author_sort Bergman, Jorieke E. H.
collection PubMed
description Limb reduction defects (LRDs) that affect multiple limbs are considered to be more often heritable, but only few studies have substantiated this. We aimed to investigate if an etiological diagnosis (genetic disorder or clinically recognizable disorder) is more likely to be made when multiple limbs are affected compared to when only one limb is affected. We used data from EUROCAT Northern Netherlands and included 391 fetuses and children with LRDs born in 1981–2017. Cases were classified as having a transverse, longitudinal (preaxial/postaxial/central/mixed), intercalary, or complex LRD of one or more limbs and as having an isolated LRD or multiple congenital anomalies (MCA). We calculated the probability of obtaining an etiological diagnosis in cases with multiple affected limbs versus one affected limb using relative risk (RR) scores and Fisher's exact test. We showed that an etiological diagnosis was made three times more often when an LRD occurred in multiple limbs compared to when it occurred in one limb (RR 2.9, 95% CI 2.2–3.8, p < 0.001). No genetic disorders were found in isolated cases with only one affected limb, whereas a genetic disorder was identified in 16% of MCA cases with one affected limb. A clinically recognizable disorder was found in 47% of MCA cases with one affected limb. Genetic counseling rates were similar. We conclude that reduction defects of multiple limbs are indeed more often heritable. Genetic testing seems less useful in isolated cases with one affected limb, but is warranted in MCA cases with one affected limb.
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spelling pubmed-77568932020-12-28 Etiological diagnosis in limb reduction defects and the number of affected limbs: A population‐based study in the Northern Netherlands Bergman, Jorieke E. H. Löhner, Katharina van der Sluis, Corry K. Rump, Patrick de Walle, Hermien E. K. Am J Med Genet A Original Articles Limb reduction defects (LRDs) that affect multiple limbs are considered to be more often heritable, but only few studies have substantiated this. We aimed to investigate if an etiological diagnosis (genetic disorder or clinically recognizable disorder) is more likely to be made when multiple limbs are affected compared to when only one limb is affected. We used data from EUROCAT Northern Netherlands and included 391 fetuses and children with LRDs born in 1981–2017. Cases were classified as having a transverse, longitudinal (preaxial/postaxial/central/mixed), intercalary, or complex LRD of one or more limbs and as having an isolated LRD or multiple congenital anomalies (MCA). We calculated the probability of obtaining an etiological diagnosis in cases with multiple affected limbs versus one affected limb using relative risk (RR) scores and Fisher's exact test. We showed that an etiological diagnosis was made three times more often when an LRD occurred in multiple limbs compared to when it occurred in one limb (RR 2.9, 95% CI 2.2–3.8, p < 0.001). No genetic disorders were found in isolated cases with only one affected limb, whereas a genetic disorder was identified in 16% of MCA cases with one affected limb. A clinically recognizable disorder was found in 47% of MCA cases with one affected limb. Genetic counseling rates were similar. We conclude that reduction defects of multiple limbs are indeed more often heritable. Genetic testing seems less useful in isolated cases with one affected limb, but is warranted in MCA cases with one affected limb. John Wiley & Sons, Inc. 2020-09-21 2020-12 /pmc/articles/PMC7756893/ /pubmed/32954639 http://dx.doi.org/10.1002/ajmg.a.61875 Text en © 2020 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Bergman, Jorieke E. H.
Löhner, Katharina
van der Sluis, Corry K.
Rump, Patrick
de Walle, Hermien E. K.
Etiological diagnosis in limb reduction defects and the number of affected limbs: A population‐based study in the Northern Netherlands
title Etiological diagnosis in limb reduction defects and the number of affected limbs: A population‐based study in the Northern Netherlands
title_full Etiological diagnosis in limb reduction defects and the number of affected limbs: A population‐based study in the Northern Netherlands
title_fullStr Etiological diagnosis in limb reduction defects and the number of affected limbs: A population‐based study in the Northern Netherlands
title_full_unstemmed Etiological diagnosis in limb reduction defects and the number of affected limbs: A population‐based study in the Northern Netherlands
title_short Etiological diagnosis in limb reduction defects and the number of affected limbs: A population‐based study in the Northern Netherlands
title_sort etiological diagnosis in limb reduction defects and the number of affected limbs: a population‐based study in the northern netherlands
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756893/
https://www.ncbi.nlm.nih.gov/pubmed/32954639
http://dx.doi.org/10.1002/ajmg.a.61875
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