Author:
Beckers Albert,Lodish Maya Beth,Trivellin Giampaolo,Rostomyan Liliya,Lee Misu,Faucz Fabio R,Yuan Bo,Choong Catherine S,Caberg Jean-Hubert,Verrua Elisa,Naves Luciana Ansaneli,Cheetham Tim D,Young Jacques,Lysy Philippe A,Petrossians Patrick,Cotterill Andrew,Shah Nalini Samir,Metzger Daniel,Castermans Emilie,Ambrosio Maria Rosaria,Villa Chiara,Strebkova Natalia,Mazerkina Nadia,Gaillard Stéphan,Barra Gustavo Barcelos,Casulari Luis Augusto,Neggers Sebastian J,Salvatori Roberto,Jaffrain-Rea Marie-Lise,Zacharin Margaret,Santamaria Beatriz Lecumberri,Zacharieva Sabina,Lim Ee Mun,Mantovani Giovanna,Zatelli Maria Chaira,Collins Michael T,Bonneville Jean-François,Quezado Martha,Chittiboina Prashant,Oldfield Edward H,Bours Vincent,Liu Pengfei,de Herder Wouter W,Pellegata Natalia,Lupski James R,Daly Adrian F,Stratakis Constantine A
Abstract
X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the geneGPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2–3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management.
Subject
Cancer Research,Endocrinology,Oncology,Endocrinology, Diabetes and Metabolism
Cited by
143 articles.
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