ECE2018 ePoster Presentations Adrenal and Neuroendocrine Tumours (28 abstracts)
The changing of clinical scenario in three consecutive generations of a Brazilian Family with Von Hippel-Lindau disease
Alice Violante 1 , Jorge Lima 2 , Paula Soares 2 , Ana Macedo 2 , Silvio Cunha Neto 3 , Erika Naliato 4 , João Migowski 5 , Amanda Alecrim 5 , Vinicius Lima 6 , Denise Carvalho 6 & Delmar Lourenço 7
1Endocrine Unit, Medical School, Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro – UFRJ, Rio de Janeiro, Brazil; 2Instituto de Patologia e Imunologia Molecular da Universidade do Porto-IPATIMUP, Porto, Portugal; 3Surgery Unit, Medical School, Hospital Universitario Clementino Fraga Filho -UFRJ, Rio de Janeiro, Bouvet Island; 4Centro de Estudos Ricardo A T Castilho da Associação Medica de Teresopolis, Teresopolis, Brazil; 5Medical School – UFRJ, Rio de Janeiro, Brazil; 6Fisiologia Endocrina -Instituto de Biofisica Medica Carlos Chagas Filho – UFRJ, Rio de Janeiro, Brazil; 7Hospital das Clinicas, Medical School, Universidade de São Paulo, São Paulo, Brazil.
Background: Von Hippel Lindau Disease (VHL) is an autosomal dominant inherited syndrome characterized by high susceptibility to the development of a wide spectrum of benign and malignant, endocrine and non-endocrine neoplasias in diverse organs of patients harboring a germline mutation in VHL tumor suppressor gene. The major clinical manifestations of VHL are brain, cerebellar and spinal cord hemangioblastoma, retinal angioma, pheochromocytoma, renal cell carcinoma and/or cysts and pancreatic neuroendocrine tumor and/or cysts.
Results: From a parental generation whose clinical data are unavailable, two sisters from the 2nd generation (Sibling 1 and Sibling 2) died from brain tumors without pathologic or molecular diagnosis. The first (S1-2ndG) had five children (females =4) and the second (S2-2ndG) had two daughters. From S1-2ndG, 4 siblings were clinically and genetically investigated (3 females; 1 male): two sisters had multifocal pancreatic neuroendocrine tumor and cysts with one of them (S1-3rdG) presenting bilateral pheochromocytoma, while the other (S2-3rdG) had brain hemangioblastoma, endolymphatic sac tumor and retinal angioma. Their brother (S3-3rdG) was diagnosed with retinal angioma and renal cysts, while the 3rd sister (S4-3rdG) was asymptomatic, and negative for the VHL p.Asn78Ser (c.233A>G; exon 1) mutation that was found in all the affected members of this family. From S2-2ndG, one of the two sisters (S5-3rdG) who married with her affected cousin (S3-3rdG) harbored the same mutation found in their cousins and her husband. Exams directed to VHL-related tumors were performed after positive genetic testing, but two at-risk members (S5-3rdG and S6-3rdG) refused molecular diagnosis. From the 4th generation, five at-risk members with ages between 5 and 16 y-old were genetically investigated and all of them were non-VHL mutation carriers.
Conclusions: The combined molecular and clinical diagnosis has the potential of reducing VHL-related morbidity/mortality by offering an extensive periodic screening schedule directed to early detection and treatment of tumors in affected VHL patients and asymptomatic VHL-positive carriers. In addition, negative-VHL carriers are excluded of this preventive program after genetic counseling. Indeed, in these three generations from one VHL family, we could document the natural history of the syndrome in deceased members from the second generation, the impact of clinical diagnosis in the third-generation members and, finally, the benefits of genetic counseling to VHL-negative mutation children from the 4th generation.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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