Oncological implications of RET gene mutations in Hirschsprung's disease.

BACKGROUND: Germline mutations of the RET proto-oncogene identical to those found in the tumour predisposition syndrome multiple endocrine neoplasia type 2A (MEN2A), were detected in 2.5-5% of sporadic and familial cases of Hirschsprung's disease. Some patients with Hirschsprung's disease may therefore be exposed to a highly increased risk of tumours. AIMS: To define clinical use of RET gene testing in Hirschsprung's disease and related patient management from an oncological point of view. METHODS: Sixty patients with Hirschsprung's disease were screened for RET mutations. In three, MEN2A type RET mutations were detected. Case reports for these three patients are presented. RESULTS AND CONCLUSIONS: Only 22 families or sporadic patients with Hirschsprung's disease and MEN2A type RET mutations have been reported. Therefore, it is difficult to predict tumour risk for patients with familial or sporadic Hirschsprung's disease, and their relatives, who carry these mutations. For these mutation carriers, periodic screening for tumours as in MEN2A is advised, but prophylactic thyroidectomy is offered hesitantly. RET gene testing in familial or sporadic Hirschsprung's disease is not recommended at present outside a complete clinical research setting. In combined MEN2A/Hirschsprung's disease families RET gene testing, tumour screening, and prophylactic thyroidectomy are indicated as in MEN2A.

Psychological risks of genetically testing children for a hereditary cancer syndrome.

Parents in families with a hereditary cancer syndrome are often familiar with periodical clinical testing of both themselves and their children. Genetic testing is an additional early diagnostic option that is becoming available for an increasing number of hereditary cancer syndromes. Participants in genetic counseling programs for cancer syndromes are often parents who apply for their children. If a child is identified as a carrier of a specific disease-causing gene mutation, sometimes its parents must decide on when it will be treated can treatment be postponed until expression of the disease or should the child receive presymptomatic surgery? We discuss some of the possible risks of genetically testing children: distress as a result of ambivalent feelings towards testing, preoccupation with disease-related signs, changes in family interactions, the burdening prospect of a future disease and medicalization of the carrier-child.

Psychosocial consequences of DNA analysis for MEN type 2.

Multiple endocrine neoplasia type 2 (MEN-2) is characterized by medullary thyroid carcinoma in combination with pheochromocytomas and, sometimes, parathyroid adenomas. Since 1993, the psychosocial implications of DNA analysis for MEN-2 have been studied in the Netherlands. This article summarizes the first results of that study. Individuals who applied for DNA analysis cited the need to reduce uncertainty as the major reason for wanting the test. An unfavorable test outcome resulted in anxiety and depression but also relief. Immediate preventive treatment was preferred to continued periodic screening. Carriers were preoccupied with disease-related complaints, and identified with other carriers and MEN-2 patients. A favorable test led, in most applicants and partners, to both relief and worry. Some noncarriers felt guilty and isolated from their families. One year after counseling, participants reported fewer psychosomatic complaints.