Major Genetic Syndromes
Table 7. Recommended Screening Intervals by Spigelman Stage continued...
Hepatoblastoma is a rare, rapidly progressive, and usually fatal childhood malignancy that, if confined to the liver, can be cured by radical surgical resection. Multiple cases of hepatoblastoma have been described in children with an APC mutation.[108,109,110,111,112,113,114,115,116,117] Some series have also demonstrated LOH of APC in these tumors.[109,111,118] No specific genotype-phenotype correlations have been identified in FAP patients with hepatoblastoma. Although lacking level 1 evidence, a consensus panel has recommended abdominal examination, abdominal ultrasound, and measurement of serum alpha fetoprotein every 3 to 6 months for the first 5 years of life in children with a predisposition to FAP.[84,120]
The constellation of CRC and brain tumors has been referred to as Turcot syndrome; however, Turcot syndrome is molecularly heterogeneous. Molecular studies have demonstrated that colon polyposis and medulloblastoma are associated with mutations in APC, while colon cancer and glioblastoma are associated with mutations in mismatch repair (MMR) genes.
There are several reports of other extracolonic tumors associated with FAP, but whether these are simply coincidence or actually share a common molecular genetic origin with the colonic tumors is not always evident. Some of these reports have demonstrated LOH or a mutation of the wild-type APC allele in extracolonic tumors in FAP patients, which strengthens the argument for their inclusion in the FAP syndrome.
Genetic testing for FAP
APC gene testing is now commercially available and has led to changes in management guidelines, particularly for those whose tests indicate they are not mutation carriers. Presymptomatic genetic diagnosis of FAP in at-risk individuals has been feasible with linkage  and direct detection  of APC mutations. These tests require a small sample (<10 cc) of blood in which the lymphocyte DNA is tested. If one were to use linkage analysis to identify gene carriers, ancillary family members, including more than one affected individual, would need to be studied. With direct detection, fewer family members' blood samples are required than for linkage analysis, but the specific mutation must be identified in at least one affected person by DNA mutation analysis or sequencing. The detection rate is approximately 80% using sequencing alone.