CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Clinical and genetic findings of Paraganglioma/Pheochromocytoma Syndromes associated with SDHB and SDHD mutations (Pgl4 and PGL1)
Autor/es:
SANSO GABRIELA ; VIEITES ANA; LEVIN GLORIA; DAHIA PATRICIA; BARONTINI MARTA
Lugar:
Montevideo
Reunión:
Congreso; XXIII Annual Meeting of the Pediatrics Endocrinology Latinoamerican Society; 2012
Institución organizadora:
SLEP
Resumen:
Pgl4 and Pgl1 are related to gene mutations encoding succinate dehydrogenase subunits B (SDHB) and D (SDHD). Pheochromocytomas and Pgl occur in both syndromes. The genetic findings and the differences in clinical features of 19 index cases with Pgl4, (twelve youngster 8-17y and 7 adults) and 3 Pgl1 adults, with 1-12 years of follow up (median=4) are described.All Pgl4 and 2 Pgl1 presented symptoms caused by hypersecretion of catecholamines with NA and VMA increase. 5/19 Pgl4 presented adrenal and 15/19 extra-adrenal pheo, 8/19 were malignant. 1/3 Pgl1 presented adrenal pheo and all of them developed head and neck pgl. PCR followed by direct sequencing was performed to characterize SDH mutations. The SDHB analysis showed: 5 misense mutations:#S198R(1), #L65R(1),#Q235*(1),#E178*(1), 1 Frameshift:c166_170delCCTA(10), 1 Del 1-2 and 2 intron variations, IVS2+33G>A and IVS2+35G>A. The SDHD mutations were: c341_2Atdel, c57_Gdel and c217dup. Five new variants (#) were considered pathogenic based on predictionstools available online. 10/23 SDHB relatives studied were carriers, 2-10 had clinical disease. 18/29 SDHD relatives were carriers, 6/18 had head and neck pgl. The frequency of the delection c166_170delCCTCA was remarkably higer than reproted so far, (p<0.001, Fisher Exact test). Age of diagnosis, phenotypes and rate of malignancy of SDHB and SDHD was different with higher incidence in youngster and risk of malignancy in Pgl4, and higher frequency of head and neck tumors in SDHD.