Hirschsprung's disease and medullary carcinoma of the thyroids: two diseases in a monogenetic disorder

• Published in: Cirugía pediátrica Vol. 25; no. 2; pp. 87 - 90
• Main Authors: Olivares Muñoz, M, Julià Masip, M V, Oriola, J, Martorell Sampol, L, Parareda Sallés, A, Ribó Cruz, J M
• Format: Journal Article
• Language: Spanish
• Published: Spain 01.04.2012
• Subjects: Carcinoma, Medullary - complications; Carcinoma, Medullary - genetics; Child, Preschool; Female; Hirschsprung Disease - complications; Hirschsprung Disease - genetics; Humans; Male; Mutation; Proto-Oncogene Proteins c-ret - genetics; Thyroid Neoplasms - complications; Thyroid Neoplasms - genetics
• ISSN: 0214-1221

The most common gene involved in Hirschsprung's disease (HD) is protooncogene RET. More than 100 mutations of this gene have been described associated with HD. The mutations that change a cysteine with another aminoacid (mainly in exons 10 and 11) give a risk of familial medullary thyroid carcinoma (FTMC) and MEN 2A. These mutations are found in 5% of patients with HD and have an autosomal dominant inheritance. The FTMC is aggressive and the prophylactic thyroidectomy is the best treatment. We present our results in screening for RET protooncogene mutations associated with TMC in patients with HD. We have treated 40 patients with HD in the last 15 years. We have classified the patients into two groups: A) high risk of RET protooncogene mutation associated with FTMC (family history of HD, long-segment and/or associated syndromes) and B) low risk (rectosigmoid involvement). We have identified the exons 7, 8, 9, 10, 11, 13, 14 and 15 of the RET protooncogene in 12 of 15 children from group A and 6 from 25 from group B. We have found the p.Cys620Ser mutation (exon 10) in a girl from group A (long-segment). In the family study, we have found the same mutation in her mother, her oncle and her cousin. The comprehensive management of children with HD requires screening for RET protooncogene mutations associated with FTMC. In the first-degree relatives of children with a mutation risk, screening is required.