Underlying genetic factors of the VATER/VACTERL association with special emphasis on the "Renal" phenotype

Heiko Reutter; Alina C Hilger; Friedhelm Hildebrandt; Michael Ludwig

doi:10.1007/s00467-016-3335-3

Underlying genetic factors of the VATER/VACTERL association with special emphasis on the "Renal" phenotype

Pediatr Nephrol. 2016 Nov;31(11):2025-33. doi: 10.1007/s00467-016-3335-3. Epub 2016 Feb 8.

Authors

Heiko Reutter^{1

2}, Alina C Hilger³, Friedhelm Hildebrandt⁴, Michael Ludwig⁵

Affiliations

¹ Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. [email protected].
² Department of Neonatology and Pediatric Intensive Care, Children's Hospital-University of Bonn, Bonn, Germany. [email protected].
³ Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
⁴ Department of Medicine, Boston Children's Hospital-Harvard Medical School, Boston, MA, USA.
⁵ Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.

Abstract

The acronym VATER/VACTERL association (OMIM #192350) refers to the rare non-random co-occurrence of the following component features (CFs): vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). According to epidemiological studies, the majority of patients with VATER/VACTERL association present with a "Renal" phenotype comprising a large spectrum of congenital renal anomalies. This finding is supported by evidence linking all of the human disease genes for the VATER/VACTERL association identified to date, namely, FGF8, FOXF1, HOXD13, LPP, TRAP1, and ZIC3, with renal malformations. Here we review these genotype-phenotype correlations and suggest that the elucidation of the genetic causes of the VATER/VACTERL association will ultimately provide insights into the genetic causes of the complete spectrum of congenital renal anomalies per se.

Keywords: Association; Genetics; Renal; VACTERL; VATER.

Publication types

Review

MeSH terms

Abnormalities, Multiple / epidemiology
Abnormalities, Multiple / genetics*
Anal Canal / abnormalities*
Anus, Imperforate / epidemiology
Anus, Imperforate / genetics*
Cytoskeletal Proteins / genetics
Esophagus / abnormalities*
Fibroblast Growth Factor 8 / genetics
Forkhead Transcription Factors / genetics
Genotype
HSP90 Heat-Shock Proteins / genetics
Heart Defects, Congenital / epidemiology
Heart Defects, Congenital / genetics*
Homeodomain Proteins / genetics
Humans
Kidney / abnormalities*
LIM Domain Proteins / genetics
Limb Deformities, Congenital / epidemiology
Limb Deformities, Congenital / genetics*
Mutation
Phenotype
Prevalence
Radius / abnormalities*
Rare Diseases / epidemiology
Rare Diseases / genetics*
Spine / abnormalities*
Trachea / abnormalities*
Transcription Factors / genetics

Substances

Cytoskeletal Proteins
FGF8 protein, human
FOXF1 protein, human
Forkhead Transcription Factors
HOXD13 protein, human
HSP90 Heat-Shock Proteins
Homeodomain Proteins
LIM Domain Proteins
LPP protein, human
TRAP1 protein, human
Transcription Factors
ZIC3 protein, human
Fibroblast Growth Factor 8

Supplementary concepts

VACTERL association
VATER association

Grants and funding

R01 DK088767/DK/NIDDK NIH HHS/United States