Search Results
You are looking at 1 - 5 of 5 items for
- Author: Misu Lee x
- Refine by access: All content x
Search for other papers by Misu Lee in
Google Scholar
PubMed
Search for other papers by Amelie Lupp in
Google Scholar
PubMed
Search for other papers by Nigel Mendoza in
Google Scholar
PubMed
Search for other papers by Niamh Martin in
Google Scholar
PubMed
Search for other papers by Rudi Beschorner in
Google Scholar
PubMed
Search for other papers by Jürgen Honegger in
Google Scholar
PubMed
Search for other papers by Jürgen Schlegel in
Google Scholar
PubMed
Search for other papers by Talia Shively in
Google Scholar
PubMed
Search for other papers by Elke Pulz in
Google Scholar
PubMed
Search for other papers by Stefan Schulz in
Google Scholar
PubMed
Search for other papers by Federico Roncaroli in
Google Scholar
PubMed
Search for other papers by Natalia S Pellegata in
Google Scholar
PubMed
Gonadotroph pituitary adenomas (GPAs) often present as invasive macroadenomas not amenable to complete surgical resection. Radiotherapy is the only post-operative option for patients with large invasive or recurrent lesions. No medical treatment is available for these patients. The somatostatin analogs (SSAs) octreotide and lanreotide that preferentially target somatostatin receptor type 2 (SSTR2) have little effect on GPAs. It is widely accepted that the expression of specific SSTR subtypes determines the response to SSAs. Given that previous studies on mRNA and protein expression of SSTRs in GPAs have generated conflicting results, we investigated the expression of SSTR2, SSTR3, and SSTR5 (the main targets of available SSAs) in a clinically and pathologically well-characterized cohort of 108 patients with GPAs. A total of 118 samples were examined by immunohistochemistry using validated and specific MABs. Matched primary and recurrent tissues were available for ten patients. The results obtained were validated in an independent cohort of 27 GPAs. We observed that SSTR3 was significantly more abundant than SSTR2 (P<0.0001) in GPAs, while full-length SSTR5 was only expressed in few tumors. Expression of SSTR3 was similar in primary and recurrent adenomas, was high in potentially aggressive lesions, and did not change significantly in adenomas that recurred after irradiation. In conclusion, low levels of expression of SSTR2 may account for the limited response of GPAs to octreotide and lanreotide. Given the potent anti-proliferative, pro-apoptotic, and anti-angiogenic activities of SSTR3, targeting this receptor with a multireceptor ligand SSA such as pasireotide may be indicated for potentially aggressive GPAs.
Search for other papers by Misu Lee in
Google Scholar
PubMed
Search for other papers by Ninelia Minaskan in
Google Scholar
PubMed
Search for other papers by Tobias Wiedemann in
Google Scholar
PubMed
Search for other papers by Martin Irmler in
Google Scholar
PubMed
German Center for Diabetes Research (DZD), Neuherberg, Germany
Technische Universität München, Chair of Experimental Genetics, Freising, Germany
Search for other papers by Johannes Beckers in
Google Scholar
PubMed
Search for other papers by Behrooz H Yousefi in
Google Scholar
PubMed
Search for other papers by Georgios Kaissis in
Google Scholar
PubMed
Search for other papers by Rickmer Braren in
Google Scholar
PubMed
Search for other papers by Iina Laitinen in
Google Scholar
PubMed
Search for other papers by Natalia S Pellegata in
Google Scholar
PubMed
Pheochromocytomas (PCCs) are mostly benign tumors, amenable to complete surgical resection. However, 10–17% of cases can become malignant, and once metastasized, there is no curative treatment for this disease. Given the need to identify the effective therapeutic approaches for PCC, we evaluated the antitumor potential of the dual-PI3K/mTOR inhibitor BEZ235 against these tumors. We employed an in vivo model of endogenous PCCs (MENX mutant rats), which closely recapitulate the human tumors. Mutant rats with PCCs were treated with 2 doses of BEZ235 (20 and 30 mg/kg), or with placebo, for 2 weeks. Treatment with BEZ235 induced cytostatic and cytotoxic effects on rat PCCs, which could be appreciated by both staining the tumors ex vivo with appropriate markers and non-invasively by functional imaging (diffusion-weighted magnetic resonance imaging) in vivo. Transcriptomic analyses of tumors from rats treated with BEZ235 or placebo-identified potential mediators of therapy response were performed. Slc6a2, encoding the norepinephrine transporter (NET), was downregulated in a dose-dependent manner by BEZ235 in rat PCCs. Moreover, BEZ235 reduced Slc6a2/NET expression in PCC cell lines (MPC) also. Studies of a BEZ235-resistant derivative of the MPC cell line confirmed that the reduction of NET expression associates with the response to the drug. Reduction of NET expression after BEZ235 treatment in vivo could be monitored by positron emission tomography (PET) using a tracer targeting NET. Altogether, here we demonstrate the efficacy of BEZ235 against PCC in vivo, and show that functional imaging can be employed to monitor the response of PCC to PI3K/mTOR inhibition therapy.
Search for other papers by Tomoko Sekiya in
Google Scholar
PubMed
Search for other papers by Marcello D Bronstein in
Google Scholar
PubMed
Search for other papers by Katiuscia Benfini in
Google Scholar
PubMed
Search for other papers by Viviane C Longuini in
Google Scholar
PubMed
Search for other papers by Raquel S Jallad in
Google Scholar
PubMed
Search for other papers by Marcio C Machado in
Google Scholar
PubMed
Search for other papers by Tatiana D Goncalves in
Google Scholar
PubMed
Search for other papers by Luciana H Osaki in
Google Scholar
PubMed
Search for other papers by Leonardo Higashi in
Google Scholar
PubMed
Endocrine Genetics Unit LIM-25, Neuroendocrinology Unit, Adrenal Unit (LIM-42), Experimental Oncology Laboratory (LIM-24), Nursing School, School of Public Health, Endocrinology Division, Brigadeiro Hospital, Federal University of Sao Paulo, Human Genome Research Center, Department of Cell and Developmental Biology, Instituto do Cérebro, National Institute of Aging, Institute of Pathology, School of Medicine, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil
Search for other papers by Jose Viana-Jr in
Google Scholar
PubMed
Search for other papers by Claudio Kater in
Google Scholar
PubMed
Search for other papers by Misu Lee in
Google Scholar
PubMed
Search for other papers by Sara Molatore in
Google Scholar
PubMed
Search for other papers by Guilherme Francisco in
Google Scholar
PubMed
Search for other papers by Roger Chammas in
Google Scholar
PubMed
Search for other papers by Michel S Naslavsky in
Google Scholar
PubMed
Endocrine Genetics Unit LIM-25, Neuroendocrinology Unit, Adrenal Unit (LIM-42), Experimental Oncology Laboratory (LIM-24), Nursing School, School of Public Health, Endocrinology Division, Brigadeiro Hospital, Federal University of Sao Paulo, Human Genome Research Center, Department of Cell and Developmental Biology, Instituto do Cérebro, National Institute of Aging, Institute of Pathology, School of Medicine, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil
Search for other papers by David Schlesinger in
Google Scholar
PubMed
Search for other papers by Patricia Gama in
Google Scholar
PubMed
Search for other papers by Yeda A O Duarte in
Google Scholar
PubMed
Search for other papers by Maria Lucia Lebrão in
Google Scholar
PubMed
Search for other papers by Mayana Zatz in
Google Scholar
PubMed
Search for other papers by Osorio Meirelles in
Google Scholar
PubMed
Search for other papers by Bernardo Liberman in
Google Scholar
PubMed
Search for other papers by Maria Candida B V Fragoso in
Google Scholar
PubMed
Search for other papers by Sergio P A Toledo in
Google Scholar
PubMed
Search for other papers by Natalia S Pellegata in
Google Scholar
PubMed
Search for other papers by Rodrigo A Toledo in
Google Scholar
PubMed
Abstract
Germline mutations in p27 kip1 are associated with increased susceptibility to multiple endocrine neoplasias (MEN) both in rats and humans; however, the potential role of common polymorphisms of this gene in endocrine tumor susceptibility and tumorigenesis remains mostly unrecognized. To assess the risk associated with polymorphism rs2066827 (p27-V109G), we genotyped a large cohort of Brazilian patients with sporadic endocrine tumors (pituitary adenomas, n=252; pheochromocytomas, n=125; medullary thyroid carcinoma, n=51; and parathyroid adenomas, n=19) and 885 population-matched healthy controls and determined the odds ratios and 95% CIs. Significant associations were found for the group of patients with pituitary adenomas (P=0.01), particularly for those with ACTH-secreting pituitary adenomas (P=0.005). In contrast, no association was found with GH-secreting pituitary tumors alone or with the sporadic counterpart of MEN2-component neoplasias. Our in vitro analyses revealed increased colony formation and cell growth rate for an AtT20 corticotropin mouse cell line overexpressing the p27-V109G variant compared with cells transfected with the WT p27. However, the genotypic effects in genetic and in vitro approaches were divergent. In accordance with our genetic data showing specificity for ACTH-secreting pituitary tissues, the overexpression of p27-V109G in a GH3 somatotropin rat cell line resulted in no difference compared with the WT. Pituitary tumors are one of the major clinical components of syndromes associated with the p27 pathogenic mutations MENX and MEN4. Our genetic and in vitro data indicate that the common polymorphism rs2066827 may play a role in corticotropinoma susceptibility and tumorigenesis through a molecular mechanism not fully understood thus far.
Search for other papers by Maria A Tichomirowa in
Google Scholar
PubMed
Search for other papers by Misu Lee in
Google Scholar
PubMed
Departments of, Endocrinology, Molecular Genetics, Institute of Pathology, Laboratory of Biochemistry and Molecular Biology, CRN2M, Department of Experimental Medicine, Neuromed, Division of Endocrinology, Department of Endocrinology, Group for Advanced Molecular Investigation, Service d'Endocrinologie, Department of Endocrinology, Unit of Endocrinology, Department of Endocrinology, Department of Endocrinology, Clinical Center of Endocrinology and Gerontology, Faculty of Medicine, Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Internal Medicine and Endocrinology, Department of Endocrinology, Service d'Endocrinologie, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart‐Tilman, University of Liège, 4000 Liège, Belgium
Search for other papers by Anne Barlier in
Google Scholar
PubMed
Search for other papers by Adrian F Daly in
Google Scholar
PubMed
Search for other papers by Ilaria Marinoni in
Google Scholar
PubMed
Departments of, Endocrinology, Molecular Genetics, Institute of Pathology, Laboratory of Biochemistry and Molecular Biology, CRN2M, Department of Experimental Medicine, Neuromed, Division of Endocrinology, Department of Endocrinology, Group for Advanced Molecular Investigation, Service d'Endocrinologie, Department of Endocrinology, Unit of Endocrinology, Department of Endocrinology, Department of Endocrinology, Clinical Center of Endocrinology and Gerontology, Faculty of Medicine, Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Internal Medicine and Endocrinology, Department of Endocrinology, Service d'Endocrinologie, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart‐Tilman, University of Liège, 4000 Liège, Belgium
Search for other papers by Marie-Lise Jaffrain-Rea in
Google Scholar
PubMed
Search for other papers by Luciana A Naves in
Google Scholar
PubMed
Search for other papers by Patrice Rodien in
Google Scholar
PubMed
Search for other papers by Vincent Rohmer in
Google Scholar
PubMed
Search for other papers by Fabio Rueda Faucz in
Google Scholar
PubMed
Search for other papers by Philippe Caron in
Google Scholar
PubMed
Search for other papers by Bruno Estour in
Google Scholar
PubMed
Search for other papers by Pierre Lecomte in
Google Scholar
PubMed
Search for other papers by Françoise Borson-Chazot in
Google Scholar
PubMed
Search for other papers by Alfred Penfornis in
Google Scholar
PubMed
Search for other papers by Maria Yaneva in
Google Scholar
PubMed
Search for other papers by Mirtha Guitelman in
Google Scholar
PubMed
Search for other papers by Emily Castermans in
Google Scholar
PubMed
Search for other papers by Catherine Verhaege in
Google Scholar
PubMed
Search for other papers by Jean-Louis Wémeau in
Google Scholar
PubMed
Search for other papers by Antoine Tabarin in
Google Scholar
PubMed
Search for other papers by Carmen Fajardo Montañana in
Google Scholar
PubMed
Search for other papers by Brigitte Delemer in
Google Scholar
PubMed
Search for other papers by Veronique Kerlan in
Google Scholar
PubMed
Search for other papers by Jean-Louis Sadoul in
Google Scholar
PubMed
Search for other papers by Christine Cortet Rudelli in
Google Scholar
PubMed
Search for other papers by Françoise Archambeaud in
Google Scholar
PubMed
Search for other papers by Sabine Zacharieva in
Google Scholar
PubMed
Search for other papers by Marily Theodoropoulou in
Google Scholar
PubMed
Search for other papers by Thierry Brue in
Google Scholar
PubMed
Departments of, Endocrinology, Molecular Genetics, Institute of Pathology, Laboratory of Biochemistry and Molecular Biology, CRN2M, Department of Experimental Medicine, Neuromed, Division of Endocrinology, Department of Endocrinology, Group for Advanced Molecular Investigation, Service d'Endocrinologie, Department of Endocrinology, Unit of Endocrinology, Department of Endocrinology, Department of Endocrinology, Clinical Center of Endocrinology and Gerontology, Faculty of Medicine, Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Internal Medicine and Endocrinology, Department of Endocrinology, Service d'Endocrinologie, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart‐Tilman, University of Liège, 4000 Liège, Belgium
Search for other papers by Alain Enjalbert in
Google Scholar
PubMed
Search for other papers by Vincent Bours in
Google Scholar
PubMed
Search for other papers by Natalia S Pellegata in
Google Scholar
PubMed
Search for other papers by Albert Beckers in
Google Scholar
PubMed
Familial isolated pituitary adenoma (FIPA) occurs in families and is unrelated to multiple endocrine neoplasia type 1 and Carney complex. Mutations in AIP account only for 15–25% of FIPA families. CDKN1B mutations cause MEN4 in which affected patients can suffer from pituitary adenomas. With this study, we wanted to assess whether mutations in CDKN1B occur among a large cohort of AIP mutation-negative FIPA kindreds. Eighty-eight AIP mutation-negative FIPA families were studied and 124 affected subjects underwent sequencing of CDKN1B. Functional analysis of putative CDKN1B mutations was performed using in silico and in vitro approaches. Germline CDKN1B analysis revealed two nucleotide changes: c.286A>C (p.K96Q) and c.356T>C (p.I119T). In vitro, the K96Q change decreased p27 affinity for Grb2 but did not segregate with pituitary adenoma in the FIPA kindred. The I119T substitution occurred in a female patient with acromegaly. p27I119T shows an abnormal migration pattern by SDS–PAGE. Three variants (p.S56T, p.T142T, and c.605+36C>T) are likely nonpathogenic because In vitro effects were not seen. In conclusion, two patients had germline sequence changes in CDKN1B, which led to functional alterations in the encoded p27 proteins in vitro. Such rare CDKN1B variants may contribute to the development of pituitary adenomas, but their low incidence and lack of clear segregation with affected patients make CDKN1B sequencing unlikely to be of use in routine genetic investigation of FIPA kindreds. However, further characterization of the role of CDKN1B in pituitary tumorigenesis in these and other cases could help clarify the clinicopathological profile of MEN4.
Search for other papers by Albert Beckers in
Google Scholar
PubMed
Search for other papers by Maya Beth Lodish in
Google Scholar
PubMed
Search for other papers by Giampaolo Trivellin in
Google Scholar
PubMed
Search for other papers by Liliya Rostomyan in
Google Scholar
PubMed
Search for other papers by Misu Lee in
Google Scholar
PubMed
Search for other papers by Fabio R Faucz in
Google Scholar
PubMed
Search for other papers by Bo Yuan in
Google Scholar
PubMed
Search for other papers by Catherine S Choong in
Google Scholar
PubMed
Search for other papers by Jean-Hubert Caberg in
Google Scholar
PubMed
Search for other papers by Elisa Verrua in
Google Scholar
PubMed
Search for other papers by Luciana Ansaneli Naves in
Google Scholar
PubMed
Search for other papers by Tim D Cheetham in
Google Scholar
PubMed
Search for other papers by Jacques Young in
Google Scholar
PubMed
Search for other papers by Philippe A Lysy in
Google Scholar
PubMed
Search for other papers by Patrick Petrossians in
Google Scholar
PubMed
Search for other papers by Andrew Cotterill in
Google Scholar
PubMed
Search for other papers by Nalini Samir Shah in
Google Scholar
PubMed
Search for other papers by Daniel Metzger in
Google Scholar
PubMed
Search for other papers by Emilie Castermans in
Google Scholar
PubMed
Search for other papers by Maria Rosaria Ambrosio in
Google Scholar
PubMed
Department of Endocrinology, Program on Developmental Endocrinology and Genetics, Helmholtz Zentrum München, Department of Molecular and Human Genetics, Department of Pediatric Endocrinology and Diabetes, Department of Clinical Genetics, Endocrinology and Diabetology Unit, Department of Endocrinology, Department of Paediatric Endocrinology, INSERM U 693, Pediatric Endocrinology Unit, Mater Medical Research Institute, Department of Endocrinology, Endocrinology and Diabetes Unit, Section of Endocrinology, Service d'Anatomie et Cytologie Pathologiques, INSERM Unité 1016, Institute of Pediatric Endocrinology, Burdenko Neurosurgery Institute, Department of Neurosurgery, Laboratorio Sabin, Section of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology and Diabetes, Department of Endocrinology, Clinical Center of Endocrinology and Gerontology, Department of Clinical Biochemistry, Skeletal Clinical Studies Unit, Laboratory of Pathology, National Institute of Neurological Disorders and Stroke, Department of Neurosurgery, Department of Pediatrics, Texas Children's Hospital, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart‐Tilman, 4000 Liège, Belgium
Department of Endocrinology, Program on Developmental Endocrinology and Genetics, Helmholtz Zentrum München, Department of Molecular and Human Genetics, Department of Pediatric Endocrinology and Diabetes, Department of Clinical Genetics, Endocrinology and Diabetology Unit, Department of Endocrinology, Department of Paediatric Endocrinology, INSERM U 693, Pediatric Endocrinology Unit, Mater Medical Research Institute, Department of Endocrinology, Endocrinology and Diabetes Unit, Section of Endocrinology, Service d'Anatomie et Cytologie Pathologiques, INSERM Unité 1016, Institute of Pediatric Endocrinology, Burdenko Neurosurgery Institute, Department of Neurosurgery, Laboratorio Sabin, Section of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology and Diabetes, Department of Endocrinology, Clinical Center of Endocrinology and Gerontology, Department of Clinical Biochemistry, Skeletal Clinical Studies Unit, Laboratory of Pathology, National Institute of Neurological Disorders and Stroke, Department of Neurosurgery, Department of Pediatrics, Texas Children's Hospital, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart‐Tilman, 4000 Liège, Belgium
Search for other papers by Chiara Villa in
Google Scholar
PubMed
Search for other papers by Natalia Strebkova in
Google Scholar
PubMed
Search for other papers by Nadia Mazerkina in
Google Scholar
PubMed
Search for other papers by Stéphan Gaillard in
Google Scholar
PubMed
Search for other papers by Gustavo Barcelos Barra in
Google Scholar
PubMed
Search for other papers by Luis Augusto Casulari in
Google Scholar
PubMed
Search for other papers by Sebastian J Neggers in
Google Scholar
PubMed
Search for other papers by Roberto Salvatori in
Google Scholar
PubMed
Search for other papers by Marie-Lise Jaffrain-Rea in
Google Scholar
PubMed
Search for other papers by Margaret Zacharin in
Google Scholar
PubMed
Search for other papers by Beatriz Lecumberri Santamaria in
Google Scholar
PubMed
Search for other papers by Sabina Zacharieva in
Google Scholar
PubMed
Search for other papers by Ee Mun Lim in
Google Scholar
PubMed
Search for other papers by Giovanna Mantovani in
Google Scholar
PubMed
Search for other papers by Maria Chaira Zatelli in
Google Scholar
PubMed
Search for other papers by Michael T Collins in
Google Scholar
PubMed
Search for other papers by Jean-François Bonneville in
Google Scholar
PubMed
Search for other papers by Martha Quezado in
Google Scholar
PubMed
Search for other papers by Prashant Chittiboina in
Google Scholar
PubMed
Search for other papers by Edward H Oldfield in
Google Scholar
PubMed
Search for other papers by Vincent Bours in
Google Scholar
PubMed
Search for other papers by Pengfei Liu in
Google Scholar
PubMed
Search for other papers by Wouter W de Herder in
Google Scholar
PubMed
Search for other papers by Natalia Pellegata in
Google Scholar
PubMed
Department of Endocrinology, Program on Developmental Endocrinology and Genetics, Helmholtz Zentrum München, Department of Molecular and Human Genetics, Department of Pediatric Endocrinology and Diabetes, Department of Clinical Genetics, Endocrinology and Diabetology Unit, Department of Endocrinology, Department of Paediatric Endocrinology, INSERM U 693, Pediatric Endocrinology Unit, Mater Medical Research Institute, Department of Endocrinology, Endocrinology and Diabetes Unit, Section of Endocrinology, Service d'Anatomie et Cytologie Pathologiques, INSERM Unité 1016, Institute of Pediatric Endocrinology, Burdenko Neurosurgery Institute, Department of Neurosurgery, Laboratorio Sabin, Section of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology and Diabetes, Department of Endocrinology, Clinical Center of Endocrinology and Gerontology, Department of Clinical Biochemistry, Skeletal Clinical Studies Unit, Laboratory of Pathology, National Institute of Neurological Disorders and Stroke, Department of Neurosurgery, Department of Pediatrics, Texas Children's Hospital, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart‐Tilman, 4000 Liège, Belgium
Department of Endocrinology, Program on Developmental Endocrinology and Genetics, Helmholtz Zentrum München, Department of Molecular and Human Genetics, Department of Pediatric Endocrinology and Diabetes, Department of Clinical Genetics, Endocrinology and Diabetology Unit, Department of Endocrinology, Department of Paediatric Endocrinology, INSERM U 693, Pediatric Endocrinology Unit, Mater Medical Research Institute, Department of Endocrinology, Endocrinology and Diabetes Unit, Section of Endocrinology, Service d'Anatomie et Cytologie Pathologiques, INSERM Unité 1016, Institute of Pediatric Endocrinology, Burdenko Neurosurgery Institute, Department of Neurosurgery, Laboratorio Sabin, Section of Endocrinology, Department of Endocrinology, Department of Endocrinology, Department of Endocrinology and Diabetes, Department of Endocrinology, Clinical Center of Endocrinology and Gerontology, Department of Clinical Biochemistry, Skeletal Clinical Studies Unit, Laboratory of Pathology, National Institute of Neurological Disorders and Stroke, Department of Neurosurgery, Department of Pediatrics, Texas Children's Hospital, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart‐Tilman, 4000 Liège, Belgium
Search for other papers by James R Lupski in
Google Scholar
PubMed
Search for other papers by Adrian F Daly in
Google Scholar
PubMed
Search for other papers by Constantine A Stratakis in
Google Scholar
PubMed
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.