Congenital Anomalies and Syndromes Predisposing to Wilms Tumor
Wilms tumor typically develops in otherwise healthy children; however, approximately 10% of children with Wilms tumor have a congenital anomaly. Children with Wilms tumor may have associated urinary tract anomalies, including hemihypertrophy, cryptorchidism, and hypospadias. Children may have a recognizable phenotypic syndrome (including overgrowth disease, aniridia, genetic malformations, and others). These syndromes have provided clues to the genetic basis of the disease. The phenotypic syndromes have been divided into overgrowth and nonovergrowth categories.
Overgrowth syndromes. Overgrowth syndromes are the result of excessive prenatal and postnatal somatic growth.[9,10] Examples of overgrowth syndromes include the following:
- Beckwith-Wiedemann syndrome (prevalence is about 1% of children with Wilms tumor).[11,12,13,14]
- Isolated hemihypertrophy (prevalence is about 2.5% of children with Wilms tumor).[11,15]
- Perlman syndrome (characterized by fetal gigantism, renal dysplasia, Wilms tumor, islet cell hypertrophy, multiple congenital anomalies, and mental retardation).
- Sotos syndrome (characterized by cerebral gigantism).
- Simpson-Golabi-Behemel syndrome (characterized by macroglossia, macrosomia, renal and skeletal abnormalities, and increased risk of embryonal cancers).
Nonovergrowth syndromes. Examples of nonovergrowth syndromes associated with Wilms tumor include the following:
- WAGR syndrome (aniridia, genitourinary anomaly, and mental retardation). The constellation of WAGR syndrome occurs in association with an interstitial deletion on chromosome 11 (del[11p13]).[17,18] (prevalence is about 0.4% of children with Wilms tumor). The incidence of bilateral Wilms tumor in children with WAGR syndrome is about 15%.
- Isolated aniridia.
- Genitourinary anomalies including hypospadias, undescended testis, and others are associated with Wilms tumor 1 (WT1) mutations (prevalence is over 6% of children with Wilms tumor). Children with pseudo-hermaphroditism and/or renal disease (glomerulonephritis or nephrotic syndrome) who develop Wilms tumor may have the Denys-Drash or Frasier syndrome (characterized by male hermaphroditism, primary amenorrhea, chronic renal failure, and other abnormalities), both of which are associated with mutations in the WT1 gene. Specifically, germline missense mutations in the WT1 gene are responsible for most Wilms tumors that occur as part of the Denys-Drash syndrome.[22,23]
- Bloom syndrome.
- Alagille syndrome.
- Trisomy 18.
- Li-Fraumeni syndrome (familial cancer syndrome).
Screening Children Predisposed to Wilms Tumor
Children with a significantly increased predisposition to develop Wilms tumor (e.g., most children with Beckwith-Wiedemann syndrome, WAGR syndrome, Denys-Drash syndrome, idiopathic hemihypertrophy, or sporadic aniridia) should be screened with ultrasound every 3 months at least until they reach age 8 years.[9,10,11,25] Children with Beckwith-Wiedemann syndrome or hemihypertrophy are at risk for developing liver and adrenal tumors. Screening with abdominal ultrasound is suggested until age 4 years; after age 4 years, imaging can be limited to renal ultrasound, which is faster and less expensive than an abdominal ultrasound. Children with Klippel-Tr�naunay syndrome, a unilateral limb overgrowth syndrome, had been considered to be at increased risk for developing Wilms tumor. The risk of Wilms tumor in children with Klippel-Tr�naunay syndrome, when assessed using the National Wilms Tumor Study (NWTS) database, was no different than in the general population and routine ultrasound surveillance is not recommended.