X-linked acrogigantism syndrome: clinical profile and therapeutic responses.

TitleX-linked acrogigantism syndrome: clinical profile and therapeutic responses.
Publication TypeJournal Article
Year of Publication2015
AuthorsBeckers, A, Lodish, MBeth, Trivellin, G, Rostomyan, L, Lee, M, Faucz, FR, Yuan, B, Choong, CS, Caberg, J-H, Verrua, E, Naves, LAnsaneli, Cheetham, TD, Young, J, Lysy, PA, Petrossians, P, Cotterill, A, Shah, NSamir, Metzger, D, Castermans, E, Ambrosio, MRosaria, Villa, C, Strebkova, N, Mazerkina, N, Gaillard, S, Barra, GBarcelos, Casulari, LAugusto, Neggers, SJ, Salvatori, R, Jaffrain-Rea, M-L, Zacharin, M, Santamaria, BLecumberri, Zacharieva, S, Lim, EMun, Mantovani, G, Zatelli, MChaira, Collins, MT, Bonneville, J-F, Quezado, M, Chittiboina, P, Oldfield, EH, Bours, V, Liu, P, de Herder, WW, Pellegata, N, Lupski, JR, Daly, AF, Stratakis, CA
JournalEndocr Relat Cancer
Date Published2015 Jun
KeywordsAcromegaly, Adenoma, Adolescent, Child, Child, Preschool, Chromosomes, Human, X, Female, Gigantism, Humans, Infant, Male, Pituitary Neoplasms, Young Adult

X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, 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.

Alternate JournalEndocr Relat Cancer
PubMed ID25712922
PubMed Central IDPMC4433400
Grant ListU54 HG006542 / HG / NHGRI NIH HHS / United States
T32 CA009071 / CA / NCI NIH HHS / United States
ZIA HD008920-02 / / Intramural NIH HHS / United States
U54HG006542 / HG / NHGRI NIH HHS / United States
U54 HD083092 / HD / NICHD NIH HHS / United States
Z01-HD008920 / HD / NICHD NIH HHS / United States
ZIA HD008920-03 / / Intramural NIH HHS / United States
R01 NS058529 / NS / NINDS NIH HHS / United States
ZIA HD008920-01 / / Intramural NIH HHS / United States

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