RESUMO
SDHB mutations are linked to the familial paraganglioma syndrome type 4 (PGL4), which is associated with predominantly extra-adrenal disease and has high metastatic rates. Despite the lower penetrance rates in carriers of SDHB mutations compared to mutations in other paraganglioma susceptibility genes, the aggressive behavior of SDHB-linked disease warrants intensive surveillance to identify and resect tumors early. Patients with similar SDHB genotypes in whom the PGL syndrome manifests often exhibit very heterogeneous phenotypes. Tumors can arise in various locations, and management can be considerably different, depending on tumor site and pathology. We present a case series of five SDHB mutation carriers over four generations from the same family to illustrate the complexities in management.
Assuntos
Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Paraganglioma Extrassuprarrenal/diagnóstico , Paraganglioma Extrassuprarrenal/genética , Succinato Desidrogenase/genética , 3-Iodobenzilguanidina , Adulto , Cromogranina A/urina , Detecção Precoce de Câncer , Éxons , Testes Genéticos , Genótipo , Heterozigoto , Humanos , Laparotomia , Masculino , Mutação , Síndromes Neoplásicas Hereditárias/radioterapia , Síndromes Neoplásicas Hereditárias/urina , Norepinefrina/urina , Paraganglioma Extrassuprarrenal/radioterapia , Paraganglioma Extrassuprarrenal/urina , Linhagem , Penetrância , Fenótipo , Cintilografia , Radiocirurgia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND OBJECTIVE: Advances in molecular biology have discovered new genes involved in the development of familial paraganglioma syndrome (PGL) including those encoding mitochondrial succinate dehydrogenase complex (SDH). We describe the diagnosis, clinical expression and genetic counselling in a family diagnosed of PGL due to a new SDHB mutation. PATIENTS AND METHOD: Genetic study by PCR-direct sequencing SDHB gene and biochemical determination in blood/urine fractionated catecholamine 24h, metanephrines and conventional (computed tomography/magnetic resonance imaging) and functional imaging ((123)I-MIBG) in all members of a family diagnosed of PGL. RESULT: DNA sequencing showed a non-described SDHB heterozygous mutation (c.287-3C>G intron3/exon4) in 5 of the subjects (71%). The estimated penetrance of the mutation's carriers was 40%, with a mean age of 35 years at diagnosis. All patients with active illness required surgical treatment after imaging and laboratory confirmation. CONCLUSIONS: We describe the pathogenicity, diagnostic algorithm, genetic counselling and clinical expression of a new SDHB mutation (c.287-3C>G) in a family diagnosed of PGL.