VACTERL/VATER association (ORPHA:887)
A rare multiple congenital anomalies characterized by the presence of at least three of the following malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities.
Epidemiology
Exact prevalence and incidence data are not available due to variable diagnostic criteria, but the association has been reported to occur in 1-9/100,000 infants, and the annual incidence has been reported to be 1/10,000 to 1/40,000 live births. No specific geographic distribution or predominance in certain populations has been found.
Clinical description
A cluster of congenital malformations may be found prenatally, perinatally, or sometimes later in life, and is usually considered to include at least three component features: vertebral defects (60-80% of patients), commonly accompanied by rib anomalies; imperforate anus/anal atresia (55-90%); cardiac defects (40-80%); tracheo-esophageal fistula (50-80%), with or without esophageal atresia; renal anomalies (50-80%) including renal agenesis, horseshoe kidney, and cystic and/or dysplastic kidneys; and limb abnormalities (40-50%). Limb defects are classically defined as radial anomalies, including thumb aplasia/hypoplasia, and have variable degrees of severity; other types of limb anomalies have also been reported. While the above malformations are considered to be the core component features (some experts consider trachea-esophageal fistula and anal atresia to be especially characteristic), many other malformations have been described in affected patients. These non-typical malformations should be used as clues in considering other possible conditions.
Etiology
VACTERL/VATER association can occur due to a variety of genetic and non-genetic causes, and there are many syndromes with overlapping features. In most individuals, the cause is unknown and the association largely occurs sporadically.
Diagnostic methods
Diagnosis of VACTERL/VATER association is based on the clinical manifestations, which may be evident prior to or after birth.
Differential diagnosis
Differential diagnosis, depending on the overall presentation, includes Baller-Gerold syndrome, CHARGE syndrome, congenital vertebral-cardiac-renal anomalies syndrome, Currarino disease, 22q11.2 microdeletion syndrome, Fanconi anemia, Feingold syndrome, Fryns syndrome, MURCS association, oculo-auriculo-vertebral spectrum, Opitz G/BBB syndrome, Pallister-Hall syndrome, Townes-Brocks syndrome, and VACTERL with hydrocephalus, as well as other conditions.
Antenatal diagnosis
The condition may be suspected prenatally, primarily based on prenatal imaging results.
Genetic counseling
The condition most commonly occurs sporadically, and the underlying causes are not known in most individuals. However, the differential diagnosis is broad, and some conditions with features of VACTERL/VATER association have known inheritance patterns.
Management and treatment
Management typically centers around surgical correction of the specific congenital anomalies (typically anal atresia, certain types of cardiac malformations, and/or tracheo-esophageal fistula) in the immediate postnatal period, followed by long-term medical management of sequelae of the congenital malformations.
Prognosis
If optimal surgical correction is achievable, the prognosis can be relatively good, though some patients will continue to be affected by their congenital malformations throughout life. Importantly, patients with VACTERL association do not tend to have neurocognitive impairment, though some conditions with overlapping features can include neurologic (and other) findings.

                            Last update: 
                            October 2023


                            - Expert reviewer(s): 
                            Dr Benjamin SOLOMON