VACTERL/VATER association

The acronym VATER/VACTERL association refers to the rare, non-random co-occurrence of vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheo-esophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). It is typically defined by the presence of at least three of these cardinal features. The aetiology has been identified only in a small fraction of patients to date, likely due to factors such as a high degree of clinical and causal heterogeneity, the largely sporadic nature of the disorder, and the presence of many similar conditions. Chromosomal abnormalities have been described in rare individual cases and proposed as possible causal factors, including: deletions of distal 13q, ring chromosome 12, and 6q; duplication on 9q;  mutations in PTEN, HOXD13, and ZIC3; and a mitochondrial substitution.

Inherited metabolic disease; Skeletal dysplasia

PTEN [HSA:5728] [KO:K01110]
HOXD13 [HSA:3239] [KO:K09298]
ZIC3 [HSA:7547] [KO:K09224]

Maternal diabetes, uterine vascular pathology, and infertility treatment

PMID:20849991 (description, gene)

Schramm C, Draaken M, Bartels E, Boemers TM, Aretz S, Brockschmidt FF, Nothen MM, Ludwig M, Reutter H

De novo microduplication at 22q11.21 in a patient with VACTERL association.

Eur J Med Genet 54:9-13 (2011)

PMID:21846383 (description)

Solomon BD

VACTERL/VATER Association.

Orphanet J Rare Dis 6:56 (2011)

PMID:22422375 (description, environmental factor)

Hilger A, Schramm C, Draaken M, Mughal SS, Dworschak G, Bartels E, Hoffmann P, Nothen MM, Reutter H, Ludwig M

Familial occurrence of the VATER/VACTERL association.

Pediatr Surg Int 28:725-9 (2012)

PMID:11748304 (gene)

Reardon W, Zhou XP, Eng C

A novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association.

J Med Genet 38:820-3 (2001)

PMID:19006232 (gene)

Garcia-Barcelo MM, Wong KK, Lui VC, Yuan ZW, So MT, Ngan ES, Miao XP, Chung PH, Khong PL, Tam PK

Identification of a HOXD13 mutation in a VACTERL patient.

Am J Med Genet A 146A:3181-5 (2008)

PMID:20452998 (gene)

Wessels MW, Kuchinka B, Heydanus R, Smit BJ, Dooijes D, de Krijger RR, Lequin MH, de Jong EM, Husen M, Willems PJ, Casey B

Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with VACTERL association: a new polyalanine disorder?

J Med Genet 47:351-5 (2010)