Table 1. Risk Factors Associated With Hepatoblastoma and Hepatocellular Carcinoma continued...
Beckwith-Wiedemann syndrome can be caused by genetic mutations and be familial, or much more commonly, by epigenetic changes and be sporadic. Either mechanism can be associated with an increased incidence of embryonal tumors, including Wilms tumor and hepatoblastoma. The gene dosage and ensuing increased expression of insulin-like growth factor 2 (IGF-2) has been implicated in the macrosomia and embryonal tumors in Beckwith-Wiedemann syndrome.[18,33] When sporadic, the types of embryonal tumors associated with Beckwith-Wiedemann syndrome have frequently also undergone somatic changes in the Beckwith-Wiedemann syndrome locus and IGF-2.[34,35] The genetics of tumors in children with hemihyperplasia have not been clearly defined.
All children with Beckwith-Wiedemann syndrome or isolated hemihyperplasia should be screened regularly by ultrasound to detect abdominal malignancies at an early stage. Screening using alpha-fetoprotein (AFP) levels, in addition to abdominal ultrasound, has helped in the early detection of hepatoblastoma in children with Beckwith-Wiedemann syndrome or hemihyperplasia. Other somatic overgrowth syndromes, such as Simpson-Golabi-Behmel syndrome, may also be associated with hepatoblastoma.
Familial adenomatous polyposis
There is an association between hepatoblastoma and familial adenomatous polyposis (FAP); children in families that carry the APC gene are at an 800-fold increased risk for hepatoblastoma. However, hepatoblastoma has been reported to occur in less than 1% of FAP family members, so ultrasound and AFP screening for hepatoblastoma in members of families with FAP has been controversial.[19,20,21,38]
A study of 50 sequential children with apparent sporadic hepatoblastoma reported five children (10%) had APC mutations. Data to date cannot rule out the possibility that predisposition to hepatoblastoma may be limited to a specific subset of APC mutations. Another study of children with hepatoblastoma found a predominance of the mutation in the 5' region of the gene, but some patients had mutations closer to the 3' region. Perhaps, screening children with hepatoblastoma for APC mutations may be appropriate, as they should be followed for potential colon cancer. This preliminary study provides some evidence that screening children with hepatoblastoma for APC mutations may be appropriate.