Presentación clínica y hallazgos genéticos en el Sindrome de Paraganglioma/Feocromocitoma familiar asociado con mutaciones en SDHB (Pgl4) y SDHD (Pgl1)

DRA GABRIELA SANSO; DRA ANA VIEITES; DRA GLORIA LEVIN; PATRICIA DAHIA; DRA MARTA BARONTINI

Montevideo

Congreso; XXIII REUNION DE LA SOCIEDAD LATINOAMERICANA DE ENDOCRINOLOGIA PEDIATRICA; 2012

SOCIEDAD LATINOAMERICANA DE ENDOCRINOLOGIA PEDIATRICA

Pgl4 and Pgl1 are related to gene mutations encoding succinato dehidrogenase 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 8-17y youngster and 7 adults) and 3 Pgl1 follow up[1-12 y(median=4) adults]are described. All Pgl4 and 2 Pgl1 presented symptoms caused of hypersecretion of catecholamines showing NAandVMA increase. 5/19 Pgl4 presented adrenal and 15/19 extra-adrenal pheo,9/19 were malignant.1/3 Pgl1 presented adrenal pheo and all of them head and neck pgl.PCR followed by direct sequencing was performed to characterize SDH mutations.The SDHB analysis showed: 5 missence mutations:*R217G(2),*S198R(1),*L65R(1),*Q235X(1),*E178X(1), 1 Frameshift: c166-170delCCTCA(10), 1 Del 1-2(1) and 2 intron sequence variations, IVS2+33G>A and IVS2+35G>A.The SDHD mutations were: c341-2ATdel, c57-Gdel and c217dup.Five new variants(*) were pathogenic using predictions tools available on-line.11/23 SDHB relatives studied were carriers, 2/11 with disease.18/29 SDHD relatives were carriers, 6/18 with head and neck pgl.The frequency of the deletion c166-170delCCTCA was remarkably higher than reported so far.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 with higher frequency of head and neck tumors in SDHD.