Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder of complex and heterogeneous etiology involving alterations in genomic imprinting. The cause of isolated hemihyperplasia (IHH) is unknown but might be due to partial or incomplete expression of BWS because both these conditions share predisposition for the same types of neoplasias. We investigated the methylation pattern of the putative imprinting control region H19DMR using peripheral blood from 12 patients, six with clinical features of BWS and six with IHH. All the patients had normal karyotypes and paternal uniparental disomy (UPD) was excluded in 10 informative cases. The normal H19DMR methylation pattern was found in eight informative patients, indicating that H19DMR methylation was not related to their condition. We suggest that the absence of neoplasias in the BWS and IHH patients studied might be related to the absence of UPD and to the presence of normal H19DMR methylation.

CONTEXTO: A síndrome de Beckwith-Wiedemann é uma doença de hipercrescimento complexa e heterogênea com alterações genéticas e epigenéticas, envolvendo imprinting genômico e predisposição ao câncer. A causa da hemi-hiperplasia isolada ainda é desconhecida e pode representar uma expressão parcial ou incompleta da síndrome de Beckwith-Wiedemann. OBJETIVOS: Revisão clínica e molecular e proposta de um protocolo experimental para utilização na prática médica. SÍNTESE DOS DADOS: Esta revisão apresenta os mecanismos genéticos e epigenéticos envolvidos na síndrome de Beckwith-Wiedemann e na hemi-hiperplasia isolada, os genes candidatos e o primeiro protocolo brasileiro, de que temos conhecimento, para a pesquisa dessas doenças. Os resultados têm sido utilizados na Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo para elucidar as bases da síndrome de Beckwith-Wiedemann/hemi-hiperplasia isolada e aplicados no Hospital das Clínicas desta Faculdade. CONCLUSÕES: A elucidação dos mecanismos etiológicos e o uso de um protocolo laboratorial para se detectar as alterações nessas doenças pode ser proveitoso no acompanhamento clínico dos pacientes e no aconselhamento genético das famílias.

CONTEXT: Beckwith-Wiedemann syndrome is a complex and heterogeneous overgrowth syndrome with genetic and epigenetic alterations, involving genomic imprinting and cancer predisposition. Isolated hemihyperplasia is of unknown cause, and it may represent a partial or incomplete expression of Beckwith-Wiedemann syndrome. OBJECTIVES: A clinical and molecular review and proposal of the use of an experimental protocol to provide a practical approach for the physician. DATA SYNTHESIS: This review demonstrates the genetic and epigenetic mechanisms involved in the Beckwith-Wiedemann syndrome and isolated hemihyperplasia, and the candidate genes. To our knowledge, this is the first Brazilian protocol for research into these disorders. The results have been used at the Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, to elucidate the basis of Beckwith-Wiedemann syndrome and isolated hemihyperplasia, and have been applied at the Hospital Universitário of the Faculdade de Medicina. CONCLUSIONS: Elucidation of the etiological mechanisms and use of a laboratory protocol to detect alterations in these disorders may be useful for guiding the management of such patients and genetic counseling of the families.