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VATER represents an acronym for Vertebral defects, Anal atresia, TracheoEsophageal fistula with esophageal atresia and Radial dysplasia. Reports of associated anomalies of the heart (Cardiac), kidney (Renal) and Limbs led to an extension of the acronym to VACTERL, the "L" representing limb anomalies in place of the "R" that first stood for "Radial" and then for "Renal". The prevalence at birth has been estimated at between 1 in 6250 and 1 in 3333. This distinct association of malformations includes esophageal atresia with fistula, anal atresia, upper preaxial limb reduction defects and costo-vertebral malformations. A subdivision into an upper and a lower group of VATER associations has been indicated, with heart malformations associated with the upper group and kidney malformations associated with the lower group. In order to identify malformations in a child as a VATER association, at least three out of the four cardinal malformations of the acronym have to be present. However, the debate as to whether VATER association is really a distinct entity is still ongoing. VATER association seems to belong to a family of related conditions among which it is a subgroup. This family would include Mullerian duct aplasia, Unilateral renal aplasia and Cervicothoracic Somite dysplasia (MURCS) association and Oculo-Auriculo-Vertebral association. Nearly all cases of VACTERL association are sporadic, with no recognized teratogen or chromosomal abnormality. Occasional single anomalies of the VACTERL association have been described in sibs or parents of the affected individuals. Only cases of VATER associated with hydrocephalus have been repeatedly reported to be genetic, with family histories indicating an autosomal or X-linked recessive mode of inheritance. An A-to-G point mutation at nucleotide position 3243 of mitochondrial DNA was found in one family where the mother and sister of a child with VATER association (who died) later developed mitochondrial cytopathy. It has also been shown that defective sonic hedgehog (Shh) signaling leads to a spectrum of developmental anomalies in mice strikingly similar to those of VATER. However, the pathogenetic hypotheses stemming from these studies cannot yet be used for genetic counselling. Parents of patients should be informed that the recurrence risk cannot be estimated but is very low, except if hydrocephalus is present. In this case, autosomal or X-linked recessive mode of inheritance should be explained. Prenatal ultrasound in further pregnancies should specifically search for anomalies of limbs, kidneys, and heart, as well as look for indirect signs of esophageal atresia. Treatment should be multidisciplinary and include management of any cardiac anomalies. |