eprintid: 24331 rev_number: 12 eprint_status: archive userid: 1589 dir: disk0/00/02/43/31 datestamp: 2018-04-30 07:34:39 lastmod: 2024-04-30 12:17:55 status_changed: 2018-04-30 07:34:39 type: article metadata_visibility: show creators_name: Dworschak, Gabriel C. creators_name: Zwink, Nadine creators_name: Schmiedeke, Eberhard creators_name: Mortazawi, Kiarasch creators_name: Märzheuser, Stefanie creators_name: Reinshagen, Konrad creators_name: Leonhardt, Johannes creators_name: Gómez, Barbara creators_name: Volk, Patrick creators_name: Rißmann, Anke creators_name: Jenetzky, Ekkehart creators_name: Reutter, Heiko title: Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance subjects: 610 divisions: 850300 divisions: 910200 abstract: 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. date: 2017 publisher: BioMed Central id_scheme: DOI ppn_swb: 1656059789 own_urn: urn:nbn:de:bsz:16-heidok-243316 language: eng bibsort: DWORSCHAKGEPIDEMIOLO2017 full_text_status: public publication: Orphanet Journal of Rare Diseases volume: 12 number: 180 place_of_pub: London pagerange: 1-5 issn: 1750-1172 citation: 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 (2017) Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance. Orphanet Journal of Rare Diseases, 12 (180). pp. 1-5. ISSN 1750-1172 document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/24331/1/13023_2017_Article_729.pdf