Updated 2006-01-18 by Juliana Leite, MD

Original text 1999-05-06 Philippe Jeanty, MD, PhD & Sandra R Silva, MD

Synonyms: VATER sequence, VATER association, VACTEL syndrome.

Definition: Initially described in 1973, the vertebral, anal, tracheoesophageal, renal and radial abnormalities (VATERL) association represents a defect in mesodermal development at the primitive streak level. More recently, this association has been expanded to include these abnormalities as well as cardiac features and a broader description of limb anomalies (VACTERL). VACTERL is a mnemonically useful acronym for a nonrandom association of malformations including V (vertebral anomalies), A (anal atresia), C (cardiac anomalies), TE (tracheoesophageal fistula or esophageal atresia), R (renal/urinary anomalies), and L (limb defect). Patients are considered to have the VACTERL association when 3 or more organ systems are involved. The most frequent defects described are tracheoesophageal fistula and anal or vertebral anomalies.

Incidence: Uncommon. Approximately 300 cases have been reported.

Etiology: Although VACTERL occurs as a sporadic event in the majority of cases, a high frequency among offspring of diabetic mothers has been observed. Some authors report that prenatal rats exposed to Adriamycin demonstrated a similar series of anomalies.

Recurrence risk: Varies from 1% to 50%

Pathogenesis: Defective mesodermal development of unknown origin, possibly a mitochondrial disorder.

Diagnosis: The association of vertebral anomalies (in particular at the lumbosacral level) and renal, heart, and radial defects constitutes the classic manifestation of VACTERL syndrome. It is well known, however that some people affected will not present all typical findings. The diagnosis can also be suspected because of polyhydramnios in the presence of a small or absent fetal stomach (the tracheoesophageal fistula), hemivertebrae or scoliosis, or limb (in particular, radius anomalies, club hand, reduction defects, and polydactylies), renal, and cardiac defects. The presence of a supernumerary rib (13 and 14 pairs thoracic, 6 to 7 lumbar) may be recognized, especially with 3D rendering. The ultrasound diagnosis of VACTERL syndrome may be accomplished early in the second trimester, if the fetus is severely affected.

Figure 1: The presence of a hemivertebra should raise the possibility of Vacterl association

Genetic anomalies: X-linked and autosomal recessive inheritance.

Differential diagnosis: Nearly half of patients with tracheoesophageal fistula will exhibit other VACTERL malformations. Townes syndrome has many similar features. Because VACTERL syndrome consists of anomalies of multiple systems, chromosomal disorders such as trisomy 18 and trisomy 13 must be excluded by karyotype study. Disorders characterized by the presence of vertebral, renal, and/or radial defects (such as thrombocytopenia absent radius syndrome, Fanconi anemia, Robert's syndrome, Holt-Oram syndrome, Nager syndrome, caudal regression syndrome, sirenomelia, müllerian duct, renal agenesis, upper limb, and rib abnormalities association, electrodactyly-ectodermal dysplasia syndrome, and Jarcho-Levin syndrome) should be considered.

Associated anomalies: Numerous. Hydrocephalus is commonly associated.

Prognosis: Poor overall but depends on the particular association of anomalies. During the last several decades the literature has reflected a steady increase in the survival of infants with the VACTERL association. Today most children with the VACTERL association survive.

Management: Termination of pregnancy can be offered before viability. Monthly sonographic monitoring of fetal growth and evaluation of the structural defects are recommended. Delivery in a tertiary center is required for prompt surgical repair and rehabilitation. The most common organ system involved is the urinary system with an upper urinary tract anomaly in more than 90% of cases. After birth patients with the VACTERL association should remain on antibiotic prophylaxis for urinary tract infection while awaiting the completion of screening. Urological follow-up is crucial since the majority of patients eventually require genitourinary intervention. Today, surgeons are more apt to correct cardiac and intestinal problems in these cases.

References:

[1] Khoury MJ, Cordero JF, Greenberg F, James LM, Erickson JD A population study of the VACTERL association: evidence for its etiologic heterogeneity. Pediatrics 1983 May;71(5):815-20

[2] Rittler M, Paz JE, Castilla EE VACTERL association, epidemiologic definition and delineation. Am J Med Genet 1996 Jun 28;63(4):529-36

[3] Jones KL. Vater association in Smith’s recognizable patterns of human malformation. WB Saunders Company – Philadelphia - 1998, pp 664-665.

[4] Damian MS, Seibel P, Schachenmayr W, Reichmann H, Dorndorf W VACTERL with the mitochondrial np 3243 point mutation. Am J Med Genet 1996 Apr 24;62(4):398-403

[5] McMullen KP, Karnes PS, Moir CR, Michels VV Familial recurrence of tracheoesophageal fistula and associated malformations. Am J Med Genet 1996 Jun 28;63(4):525-8

[6] Benacerraf BR. VATER association in Ultrasound of fetal syndromes.  Churchill Livingstone – New York - 1998, pp285-287.

[7] Froster UG, Wallner SJ, Reusche E, Schwinger E, Rehder H: VACTERL with hydrocephalus and branchial arch defects: prenatal, clinical, and autopsy findings in two brothers. Am J Med Genet 1996 Mar 15;62(2):169-72