Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant
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RESEARCH
Open Access
Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance Gabriel C. Dworschak1,2*, Nadine Zwink3,4, Eberhard Schmiedeke5, Kiarasch Mortazawi6, Stefanie Märzheuser7, Konrad Reinshagen8, Johannes Leonhardt9, Barbara Gómez10, Patrick Volk11, Anke Rißmann12, Ekkehart Jenetzky3,4,13 and Heiko Reutter1,14
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. Keywords: Anorectal malformation, ARM, Inheritance, Recurrence risk, Genetic counseling
Background Anorectal malformations (ARM) comprise a broad spectrum, ranging from mild anal anomalies to complex cloacal malformations. The estimated birth prevalence amount to 1 in 3000 live births, with a male to female ratio of 1.7 [1– 4]. Around 60% of ARM occur within the context of defined genetic syndromes or complex multiple congenital anomalies or in association with chromosomal aberrations [4, 5]. The * Correspondence: [email protected] 1 Institute of Human Genetics, University of Bonn, Bonn, Germany 2 Department of Pediatrics, Children’s Hospital, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany Full list of author information is available at the end of the article
remaining 40% are isolated ARM with its etiology remaining largely unknown. Although we previously identified 59 ARM families from the literature with at least two affected members [6], the condition is usually sporadic, with low risk of recurrence among first deg
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