ABSTRACT
The lifetime risk of breast cancer for women with Cowden syndrome is high, probably equivalent to that of BRCA gene carriers, so these women should be offered regular breast screening and possibly risk-reducing surgery. Multiple endocrine neoplasia type 2 is due to mutations in the RET gene. The main features are medullary thyroid cancer and phaeochromocytomas. Annual biochemical screening for phaeochromocytomas is by measurement of 24-hour urinary metanephrines. Caused by mutations in the CDH1 tumour suppressor gene, hereditary diffuse gastric cancer is another autosomal dominant cancer predisposition syndrome. In contrast to the dominantly inherited specific tumour syndromes previously discussed, most of the Mendelian disorders showing a generalised tendency to malignancy, especially in early life, follow autosomal recessive inheritance. The risk for further siblings of an isolated case is unlikely to exceed 1% and is probably nearer the 1 in 300 risk found overall for siblings in childhood cancer.
