TY  - JOUR
SN  - 1750-1172
SP  - 1
CY  - London
ID  - heidok24331
AV  - public
EP  - 5
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/24331/
PB  - BioMed Central
VL  - 12
Y1  - 2017///
IS  - 180
JF  - Orphanet Journal of Rare Diseases
TI  - Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance
N2  - 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.
A1  - Dworschak, Gabriel C.
A1  - Zwink, Nadine
A1  - Schmiedeke, Eberhard
A1  - Mortazawi, Kiarasch
A1  - Märzheuser, Stefanie
A1  - Reinshagen, Konrad
A1  - Leonhardt, Johannes
A1  - Gómez, Barbara
A1  - Volk, Patrick
A1  - Rißmann, Anke
A1  - Jenetzky, Ekkehart
A1  - Reutter, Heiko
ER  -