VATER/VACTERL association:  identification of seven new twin pairs, a systematic review of the literature, and a classical twin analysis.
The VATER/VACTERL association is typically defined by the presence of at least three of the following congenital malformations: vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. The identification of 14 twin pairs with an initial diagnosis of VATER/VACTERL association at our clinical centers led to the performance of a classical twin study. This involved a thorough evaluation of these 14 twin pairs and a further 55 twin pairs identified from a systematic review of the literature. The zygosity, concordance, and malformation status of all 69 twin pairs were evaluated. Twenty-four twin pairs fulfilled the criteria for inclusion in a comparison of the concordance rates between monozygous (MZ) and dizygous (DZ) twin pairs. The pairwise concordance rates were 15% [95% confidence interval (CI) 4-42%] for MZ and 18% (95% CI 5-48%) for DZ twin pairs (P=0.53). The probandwise concordance rates were 27% (95% CI 11-52%) for MZ and 31% (95% CI 13-58%) for DZ twin pairs (P=0.40). Although based on a limited number of twin pairs, the findings of the present study are consistent with the low number of familial cases reported to date, and suggest that the role of inherited genetic factors in the majority of VATER/VACTERL cases is limited.
Institute of Human Genetics Department of Neonatology, Children's Hospital Department of Genomics, Life and Brain Center Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn Department of Obstetrics and Prenatal Medicine, University Hospital Bonn, Bonn Praenatal.de - Partnership of Private Practices for Prenatal Medicine and Genetics, Düsseldorf/Cologne Department of Pediatric Surgery and Urology, Center for Child and Adolescent Health, Hospital Bremen-Mitte, Bremen, Germany Medical Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland, USA Departments of Epidemiology, Biostatistics, and HTA Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Enrika
E
Bartels
Anna C
AC
Schulz
Nicole W
NW
Mora
Daniel E
DE
Pineda-Alvarez
Charlotte H W
CHW
Wijers
Carlo M
CM
Marcelis
Rüdiger
R
Stressig
Jochen
J
Ritgen
Eberhard
E
Schmiedeke
Manuel
M
Mattheisen
Markus
M
Draaken
Per
P
Hoffmann
Alina C
AC
Hilger
Gabriel C
GC
Dworschak
Friederike
F
Baudisch
Michael
M
Ludwig
Soyhan
S
Bagci
Andreas
A
Müller
Ulrich
U
Gembruch
Annegret
A
Geipel
Christoph
C
Berg
Peter
P
Bartmann
Markus M
MM
Nöthen
Iris A L M
IALM
van Rooij
Benjamin D
BD
Solomon
Heiko M
HM
Reutter
D001006:Anus, Imperforate / Q000473:pathology*; D004200:Diseases in Twins / Q000473:pathology*; D004947:Esophagus / Q000002:abnormalities / Q000473:pathology; D006330:Heart Defects, Congenital / Q000473:pathology*; D006801:Humans; D011884:Radius / Q000002:abnormalities / Q000473:pathology; D013131:Spine / Q000002:abnormalities / Q000473:pathology; D014132:Trachea / Q000002:abnormalities / Q000473:pathology; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic