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Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance
BACKGROUND: Anorectal malformations (ARM) are rare abnormalities that occur in approximately 1 in 3000 live births with around 40% of patients presenting with isolated forms. Multiple familial cases reported, suggest underlying genetic factors that remain largely unknown. The recurrence in relatives...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729416/ https://www.ncbi.nlm.nih.gov/pubmed/29237507 http://dx.doi.org/10.1186/s13023-017-0729-7 |
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author | Dworschak, Gabriel C. Zwink, Nadine Schmiedeke, Eberhard Mortazawi, Kiarasch Märzheuser, Stefanie Reinshagen, Konrad Leonhardt, Johannes Gómez, Barbara Volk, Patrick Rißmann, Anke Jenetzky, Ekkehart Reutter, Heiko |
author_facet | Dworschak, Gabriel C. Zwink, Nadine Schmiedeke, Eberhard Mortazawi, Kiarasch Märzheuser, Stefanie Reinshagen, Konrad Leonhardt, Johannes Gómez, Barbara Volk, Patrick Rißmann, Anke Jenetzky, Ekkehart Reutter, Heiko |
author_sort | Dworschak, Gabriel C. |
collection | PubMed |
description | BACKGROUND: Anorectal malformations (ARM) are rare abnormalities that occur in approximately 1 in 3000 live births with around 40% of patients presenting with isolated forms. Multiple familial cases reported, suggest underlying genetic factors that remain largely unknown. The recurrence in relatives is considered rare, however transmission rates of ARM by affected parents have never been determined before. The inheritance pattern of ARM was investigated in our database of patients with isolated ARM. RESULTS: Within our cohort of 327 patients with isolated ARM we identified eight adult patients from eight families who had in total 16 children with their healthy spouse. Of these ten had ARM, resulting in a recurrence risk of approximately one in two live births (10 of 16; 62%). From 226 families with 459 siblings we found two affected siblings in five families. Hence, the recurrence risk of ARM among siblings is approximately one in 92 live births (5 of 459; 1.0%). CONCLUSIONS: Comparing the observed recurrence risk in our cohort with the prevalence in the general population, we see a 1500-fold increase in recurrence risk for offspring and a 32-fold increase if a sibling is affected. The recurrence risk of approximately 62% indicates an autosomal dominant mode of inheritance. Reliable figures on recurrence of ARM are becoming increasingly important since improved surgical techniques are able to maintain sexual function resulting in more offspring of patients with ARM. These data allow more precise counseling of families with ARM and support the need for genetic studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-017-0729-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5729416 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-57294162017-12-18 Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance Dworschak, Gabriel C. Zwink, Nadine Schmiedeke, Eberhard Mortazawi, Kiarasch Märzheuser, Stefanie Reinshagen, Konrad Leonhardt, Johannes Gómez, Barbara Volk, Patrick Rißmann, Anke Jenetzky, Ekkehart Reutter, Heiko Orphanet J Rare Dis Research BACKGROUND: Anorectal malformations (ARM) are rare abnormalities that occur in approximately 1 in 3000 live births with around 40% of patients presenting with isolated forms. Multiple familial cases reported, suggest underlying genetic factors that remain largely unknown. The recurrence in relatives is considered rare, however transmission rates of ARM by affected parents have never been determined before. The inheritance pattern of ARM was investigated in our database of patients with isolated ARM. RESULTS: Within our cohort of 327 patients with isolated ARM we identified eight adult patients from eight families who had in total 16 children with their healthy spouse. Of these ten had ARM, resulting in a recurrence risk of approximately one in two live births (10 of 16; 62%). From 226 families with 459 siblings we found two affected siblings in five families. Hence, the recurrence risk of ARM among siblings is approximately one in 92 live births (5 of 459; 1.0%). CONCLUSIONS: Comparing the observed recurrence risk in our cohort with the prevalence in the general population, we see a 1500-fold increase in recurrence risk for offspring and a 32-fold increase if a sibling is affected. The recurrence risk of approximately 62% indicates an autosomal dominant mode of inheritance. Reliable figures on recurrence of ARM are becoming increasingly important since improved surgical techniques are able to maintain sexual function resulting in more offspring of patients with ARM. These data allow more precise counseling of families with ARM and support the need for genetic studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-017-0729-7) contains supplementary material, which is available to authorized users. BioMed Central 2017-12-13 /pmc/articles/PMC5729416/ /pubmed/29237507 http://dx.doi.org/10.1186/s13023-017-0729-7 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Dworschak, Gabriel C. Zwink, Nadine Schmiedeke, Eberhard Mortazawi, Kiarasch Märzheuser, Stefanie Reinshagen, Konrad Leonhardt, Johannes Gómez, Barbara Volk, Patrick Rißmann, Anke Jenetzky, Ekkehart Reutter, Heiko Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance |
title | Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance |
title_full | Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance |
title_fullStr | Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance |
title_full_unstemmed | Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance |
title_short | Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance |
title_sort | epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729416/ https://www.ncbi.nlm.nih.gov/pubmed/29237507 http://dx.doi.org/10.1186/s13023-017-0729-7 |
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