Vacterl Association With Hydrocephalus

Description

VACTERL describes a constellation of congenital anomalies, including vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects; see 192350. Cases of familial VACTERL with hydrocephalus (H) have been reported with suggestion of autosomal recessive or X-linked inheritance (see 314390).

Other patients thought to have VACTERL-H, including 2 unrelated infants reported by Porteous et al. (1992), had been found to have Fanconi anemia (see 227650). Porteous et al. (1992) suggested that chromosomal breakage studies should be performed in all cases of VACTERL/VACTERL-H to rule out Fanconi anemia. Alter et al. (2007) noted that a VATER phenotype had been reported in Fanconi anemia of complementation groups A (227650), C (227645), D1 (605724), E (600901), F (603467), and G (614082). X-linked VACTERL-H is also associated with mutations in the FANCB gene (300515).

Clinical Features

Sujansky and Leonard (1983) described 3 sibs with VACTERL-H. The index case had hydrocephalus, tracheoesophageal fistula, congenital heart disease, renal hypoplasia, and bilateral agenesis of radii and thumbs. She died at 4.5 months of age. The other 2 sibs had similar malformations with in utero demise.

Iafolla et al. (1991) described 3 unrelated infants with hydrocephalus secondary to aqueductal stenosis in addition to the multisystemic features of the VATER association. One patient died secondary to respiratory failure, but 2 survived (30 months and 19 months) following early neurosurgical intervention. The authors cautioned against labeling the VATER and hydrocephalus association as a uniformly lethal or developmentally devastating disorder. The infants in neither of these reports had, it seems, anal atresia. Briard et al. (1984) also reported familial occurrence of the VACTERL association with hydrocephalus.

Evans et al. (1989) discussed VACTERL with hydrocephalus on the basis of 8 patients who had hydrocephalus and at least 2 other anomalies compatible with the VACTERL association. Their patient 7 was born to consanguineous parents.

Corsello and Giuffre (1994) described a case of VACTERL in association with hydrocephalus and occipital encephalocele. Cleft palate and severe upper limb reduction defects were present in this male child of first-cousin parents.

Molecular Genetics

Associations Pending Confirmation

Reardon et al. (2001) reported a heterozygous de novo his61-to-asp (H61D) mutation in the PTEN gene (see 601728.0030) in a child with features of VATER association with hydrocephalus, including macrocephaly, ventriculomegaly, tracheoesophageal fistula, and bilateral radial hand anomalies. Reardon et al. (2001) acknowledged that the child did not represent a classic example of the phenotype. They also emphasized the heterogeneity of this phenotype and discussed possible etiologic mechanisms.