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, W de Herder Wouter, Pellegata Natalia, Lupski James R, Daly Adrian F, Stratakis Constantine A
Department of EndocrinologyCentre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, BelgiumProgram on Developmental Endocrinology and GeneticsSection on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892-1862, USAHelmholtz Zentrum MünchenInstitute of Pathology, Neuherberg, GermanyDepartment of Molecular and Human GeneticsBaylor College of Medicine, Houston, Texas, USADepartment of Pediatric Endocrinology and DiabetesPrincess Margaret Hospital for Children, Subiaco, Western Australia, AustraliaDepartment of Clinical GeneticsCentre Hospitalier Universitaire de Liège, University of Liège, Liège, BelgiumEndocrinology and Diabetology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Clinical Sciences and Community Health, University of Milan, Milan, ItalyDepartment of EndocrinologyUniversity of Brasilia, Brasilia, BrazilDepartment of Paediatric EndocrinologyRoyal Victoria Infirmary, Newcastle University, Newcastle upon Tyne, UKINSERM U 693GHU Paris-Sud - Hôpital de Bicêtre, 78 rue du Général Leclerc, 94270 Le Kremlin-Bicêtre, FrancePediatric Endocrinology UnitUniversité Catholique de Louvain, Bruxelles, BelgiumMater Medical Research InstituteUniversity of Queensland, Brisbane, Queensland, AustraliaDepartment of EndocrinologyKEM Hospital, Mumbai, IndiaEndocrinology and Diabetes UnitBC Children's Hospital, Vancouver, British Columbia, CanadaSection of EndocrinologyDepartment of Medical Sciences, University of Ferrara, Ferrara, ItalyService d'Anatomie et Cytologie PathologiquesHopital Foch, Suresnes, FranceINSERM Unité 1016Institut Cochin, Hopital Cochin, Université Paris Descartes, Paris, FranceInstitute of Pediatric EndocrinologyEndocrinological Research Centre, Moscow
Endocr Relat Cancer. 2015 Jun;22(3):353-67. doi: 10.1530/ERC-15-0038. Epub 2015 Feb 24.
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.
X连锁肢端巨大症（X-LAG）是一种新的垂体巨人症综合征，由Xq26.3染色体上的微重复引起，该区域包含GPR101基因，该基因在垂体肿瘤中高度上调。我们进行这项研究以探索X-LAG综合征患者的临床、放射学和激素表型以及对治疗的反应。该研究纳入了18例患有X-LAG和Xq26.3染色体微重复的患者（13例散发性）。所有散发性病例都有独特的重复，两个家族的遗传模式为显性，所有Xq26.3重复携带者均受影响。患者早在2至3个月大时（中位年龄12个月）就开始快速生长。在诊断时（中位延迟27个月），患者的身高和体重标准差评分（SDS）中位数> +3.9 SDS。除了全身尺寸增加外，患儿还有肢端肥大症症状，包括肢端增大和面部粗糙。超过三分之一的病例食欲增加。由于垂体大腺瘤或增生，患者有明显的GH/IGF1分泌过多，通常还有催乳素分泌过多。通过广泛的垂体前叶切除术实现了初步的神经外科控制，但术后垂体功能减退很常见。尽管肿瘤组织中生长抑素受体亚型2有中度至高水平的表达，但使用生长抑素类似物并不容易实现控制。在使用辅助培维索孟的所有5例病例中，术后使用培维索孟导致IGF1得到控制。X-LAG是一种新的婴儿期发病的巨人症综合征，具有严重的临床表型，导致疾病管理具有挑战性。
