X-linked acrogigantism syndrome: Clinical profile and therapeutic responses

Albert Beckers, Maya Beth Lodish, Giampaolo Trivellin, Liliya Rostomyan, Misu Lee, Fabio R. Faucz, Bo Yuan, Catherine S. Choong, Jean Hubert Caberg, Elisa Verrua, Luciana Ansaneli Naves, Tim D. Cheetham, Jacques Young, Philippe A. Lysy, Patrick Petrossians, Andrew Cotterill, Nalini Samir Shah, Daniel Metzger, Emilie Castermans, Maria Rosaria AmbrosioChiara Villa, Natalia Strebkova, Nadia Mazerkina, Stéphan Gaillard, Gustavo Barcelos Barra, Luis Augusto Casulari, Sebastian J. Neggers, Roberto Salvatori, Marie Lise Jaffrain-Rea, Margaret Zacharin, Beatriz Lecumberri Santamaria, Sabina Zacharieva, Ee Mun Lim, Giovanna Mantovani, Maria Chaira Zatelli, Michael T. Collins, Jean François Bonneville, Martha Quezado, Prashant Chittiboina, Edward H. Oldfield, Vincent Bours, Pengfei Liu, Wouter W. De Herder, Natalia Pellegata, James R. Lupski, Adrian F. Daly, Constantine A. Stratakis

Research output: Contribution to journalArticle

Abstract

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 27months), 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 despitemoderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in allfive cases where it was employed. X-LAGis anewinfant-onset gigantismsyndrome thathas a severe clinical phenotype leading to challenging disease management.

Original languageEnglish (US)
Pages (from-to)353-367
Number of pages15
JournalEndocrine-related cancer
Volume22
Issue number3
DOIs
StatePublished - Jun 1 2015

Keywords

  • Duplication
  • FIPA
  • GPR101
  • Gigantism
  • Pediatric
  • Pituitary adenoma
  • X chromosome
  • X-LAG syndrome

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

Fingerprint Dive into the research topics of 'X-linked acrogigantism syndrome: Clinical profile and therapeutic responses'. Together they form a unique fingerprint.

  • Cite this

    Beckers, A., Lodish, M. B., Trivellin, G., Rostomyan, L., Lee, M., Faucz, F. R., Yuan, B., Choong, C. S., Caberg, J. H., Verrua, E., Naves, L. A., Cheetham, T. D., Young, J., Lysy, P. A., Petrossians, P., Cotterill, A., Shah, N. S., Metzger, D., Castermans, E., ... Stratakis, C. A. (2015). X-linked acrogigantism syndrome: Clinical profile and therapeutic responses. Endocrine-related cancer, 22(3), 353-367. https://doi.org/10.1530/ERC-15-0038