The impact of clinical and genetic screenings on the management of the multiple endocrine neoplasia type 1 Impacto do rastreamento clínico e genético para neoplasia endócrina múltipla tipo 1

• Published in: Clinics (São Paulo, Brazil) Brazil), 2007-01, Vol.62 (4), p.465-470
• Main Authors: Delmar Muniz Lourenço-Jr, Rodrigo Almeida Toledo, Flavia Lima Coutinho, Leontina Conceição Margarido, Sheila Aparecida Coelho Siqueira, Marcelo Augusto Cortina Gonçalves dos Santos, Fabio Luiz de Menezes Montenegro, Marcel Cerqueira Cesar Machado, Sergio Pereira Almeida Toledo
• Format: Article
• Language: English
• Subjects: Diagnóstico gênico; Gene MEN1; Genetic diagnosis; MEN1; MEN1 gene; Multiple endocrine neoplasia; NEM1; Neoplasia endócrina múltipla; Rastreamento; Screening
• ISSN: 1807-5932; 1980-5322
• DOI: 10.1590/S1807-59322007000400014

PURPOSE: To perform clinical and genetic screening for multiple endocrine neoplasia type 1 (MEN1) in patients at the Academic Hospital of the University of São Paulo School of Medicine, and to analyze its impact on clinical management of patients with MEN1. METHODS: The clinical diagnosis of MEN1 was made in accordance with the Consensus on multiple endocrine neoplasias. Mutation analysis of the entire MEN1 tumor suppressor gene and genetic screening of at-risk family members were performed by direct sequencing. To analyze the implementation of genetic diagnosis, the studied patients were separated into 3 groups: MEN1 index cases (group I), clinically diagnosed MEN1 cases (group II), and genetically diagnosed MEN1 cases (group III). RESULTS: In total, 154 individuals were clinically and genetically studied. We identified 12 different MEN1 mutations. Fifty-two MEN1 cases were identified: 13 in group I, 28 in group II, and 11 in group III. The mean age in group III (27.0 years) was significantly lower than in groups I (39.5 years) and II (42.4 years; P = 0.03 and P = 0.01, respectively). Patients in groups I and II mostly presented 2 or 3 MEN1-related tumors, while 81.8% of those in group III presented 1 or no MEN1-related tumor. Additionally, in group III, 45.4% of cases were asymptomatic, and no metastasis or death was verified. Surveillance for MEN1 mutations allowed the exclusion of 102 noncarriers, including a case of MEN1 phenocopy. CONCLUSION: Our data supports the benefits of clinical and genetic screening for multiple endocrine neoplasia type 1 in the management of this syndrome.OBJETIVOS: Realizar rastreamentos clínico e gênico para Neoplasia Endócrina Múltipla tipo 1 (NEM1) e analisar seu impacto no seguimento clínico desses pacientes no Hospital das Clínicas, SP. MÉTODOS: O diagnóstico clínico de NEM1 foi realizado de acordo com o Consenso sobre neoplasias endócrinas múltiplas. A análise genética para identificação de mutações foi realizada por sequenciamento automático de todas as regiões codificadoras e fronteiras exon/intron do gene MEN1. Os casos afetados foram sub-divididos em 3 grupos e analisados separadamente: casos-índices (grupo I), familiares diagnosticados clinicamente (grupo II) e genicamente (grupo III). RESULTADOS: Um total de 154 casos participou desse estudo, sendo 52 diagnosticados com NEM1: 13 do grupo I, 28 do grupo II e 11 do grupo III. A idade média ao diagnóstico no grupo III (27 anos) foi significativamente menor que a dos