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Orphanet J Rare Dis. 2017 Dec 13;12(1):180. doi: 10.1186/s13023-017-0729-7.

Epidemiologic analysis of families with isolated anorectal malformations suggests high prevalence of autosomal dominant inheritance.

Author information

1
Institute of Human Genetics, University of Bonn, Bonn, Germany. gabriel.dworschak@uni-bonn.de.
2
Department of Pediatrics, Children's Hospital, University of Bonn, Sigmund-Freud-Str. 25, D-53127, Bonn, Germany. gabriel.dworschak@uni-bonn.de.
3
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
4
Department of Child and Adolescent Psychiatry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
5
Department of Pediatric Surgery and Urology, Center for Child and Adolescent Health, Hospital Bremen-Mitte, Bremen, Germany.
6
Department of Pediatric Surgery, Municipal Hospital, Karlsruhe, Germany.
7
Department of Pediatric Surgery, Campus Virchow Clinic, Charité University Hospital Berlin, Berlin, Germany.
8
Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf/Altona Children's Hospital, Hamburg, Germany.
9
Department of Pediatric Surgery, St. Bernward-Hospital, Hildesheim, Germany.
10
Department of Pediatric Surgery, Children's and Youth Hospital "Auf der Bult", Hannover, Germany.
11
Department of Surgery, University of Heidelberg, Heidelberg, Germany.
12
Malformation Monitoring Centre Saxony-Anhalt, Otto-von-Guericke University, Magdeburg, Germany.
13
Child Center Maulbronn GmbH, Hospital for Pediatric Neurology and Social Pediatrics, Maulbronn, Germany.
14
Institute of Human Genetics, University of Bonn, Bonn, Germany.
15
Department of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, Bonn, Germany.

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:

ARM; Anorectal malformation; Genetic counseling; Inheritance; Recurrence risk

PMID:
29237507
PMCID:
PMC5729416
DOI:
10.1186/s13023-017-0729-7
[Indexed for MEDLINE]
Free PMC Article

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