title: Inheritance of the VATER/VACTERL association.
abstract: VATER/VACTERL association refers to the non-random co-occurrence of the following component features: vertebral defects, anal atresia, cardiac malformations, tracheoesophageal atresia, renal abnormalities, and limb defects. Recently, Solomon et al. (Hum Genet 127:731-733, 2010) observed an increased prevalence of component features among first-degree relatives of VATER/VACTERL patients suggesting that in some patients, the disorder may be inherited. To replicate these findings, we investigated 87 VATER/VACTERL patients with the presence of a minimum of three component features and their first-degree relatives (n = 271). No increase in the overall prevalence of component features was observed in first-degree relatives compared to the general population (χ² = 2.68, p = 0.10). Separate analysis for the prevalence of single component features showed a higher prevalence of tracheoesophageal fistula/atresia among first-degree relatives compared to the general population (OR 17.65, 95% CI 2.47-126.05). However, this was based on occurrence in one family only. Our findings suggest that although familial occurrence renders a genetic contribution likely, the overall risk of recurrence among the first-degree relatives of patients with VATER/VACTERL association is probably very low. Since the patients in the present study were young and no offspring could be studied, estimation of the role of de novo mutations in the development of VATER/VACTERL was not possible.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany. enrika.bartels@uni-bonn.de
authors.forename: Enrika
authors.initials: E
authors.lastname: Bartels
authors.forename: Ekkehart
authors.initials: E
authors.lastname: Jenetzky
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Solomon
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schmiedeke
authors.forename: Sabine
authors.initials: S
authors.lastname: Grasshoff-Derr
authors.forename: Dominik
authors.initials: D
authors.lastname: Schmidt
authors.forename: Stefanie
authors.initials: S
authors.lastname: Märzheuser
authors.forename: Stuart
authors.initials: S
authors.lastname: Hosie
authors.forename: Sandra
authors.initials: S
authors.lastname: Weih
authors.forename: Stefan
authors.initials: S
authors.lastname: Holland-Cunz
authors.forename: Markus
authors.initials: M
authors.lastname: Palta
authors.forename: Johannes
authors.initials: J
authors.lastname: Leonhardt
authors.forename: Mattias
authors.initials: M
authors.lastname: Schäfer
authors.forename: Christina
authors.initials: C
authors.lastname: Kujath
authors.forename: Anke
authors.initials: A
authors.lastname: Rissmann
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Nadine
authors.initials: N
authors.lastname: Zwink
mesh_terms: D000015:Abnormalities, Multiple / Q000453:epidemiology*; D001003:Anal Canal / Q000002:abnormalities; D001006:Anus, Imperforate / Q000453:epidemiology*; D015331:Cohort Studies; D004947:Esophagus / Q000002:abnormalities; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006330:Heart Defects, Congenital / Q000453:epidemiology*; D006801:Humans; D007223:Infant; D007668:Kidney / Q000002:abnormalities; D017880:Limb Deformities, Congenital / Q000453:epidemiology*; D008297:Male; D016017:Odds Ratio; D015995:Prevalence; D011884:Radius / Q000002:abnormalities; D013131:Spine / Q000002:abnormalities; D014132:Trachea / Q000002:abnormalities