title: Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.
abstract: X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome.
authors.affiliation: Department of Endocrinology, Faculty of Medicine, University of Brasilia, Brasília, Brazil. draluciananaves@gmail.com.
authors.forename: Luciana A
authors.initials: LA
authors.lastname: Naves
authors.affiliation: Departments of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Daly
authors.affiliation: Department of Neurosurgery, Federal District Base Hospital, Brasília, Brazil.
authors.forename: Luiz Augusto
authors.initials: LA
authors.lastname: Dias
authors.affiliation: Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Endocrinology, Faculty of Medicine, University of Brasilia, Brasília, Brazil.
authors.forename: Juliano Coelho Oliveira
authors.initials: JC
authors.lastname: Zakir
authors.affiliation: Laboratorio Sabin de Análises Clínicas Brasilia, Brasília, Brazil.
authors.forename: Gustavo Barcellos
authors.initials: GB
authors.lastname: Barra
authors.affiliation: Departments of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium.
authors.forename: Leonor
authors.initials: L
authors.lastname: Palmeira
authors.affiliation: Departments of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium.|Department of Pathology, Hopital Foch, Suresnes Cedex, France.
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.affiliation: Section on Endocrinology and Genetics, Program on Developmental Endocrinology & Genetics & Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Trivellin
authors.affiliation: Department of Endocrinology, Faculty of Medicine, University of Brasilia, Brasília, Brazil.
authors.forename: Armindo Jreige
authors.initials: AJ
authors.lastname: Júnior
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Brasilia, Brasília, Brazil.
authors.forename: Florêncio Figueiredo Cavalcante
authors.initials: FF
authors.lastname: Neto
authors.affiliation: Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.affiliation: Helmholtz Zentrum Munchen, Institute of Pathology, Neuherberg, Germany.
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Pellegata
authors.affiliation: Section on Endocrinology and Genetics, Program on Developmental Endocrinology & Genetics & Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
authors.affiliation: Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.|Texas Children's Hospital, Houston, TX, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.affiliation: Departments of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium. albert.beckers@chu.ulg.ac.be.
authors.forename: Albert
authors.initials: A
authors.lastname: Beckers
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002648:Child; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005877:Gigantism / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008297:Male; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome
keywords: FIPA; GPR101; Giant; Pituitary adenoma; X-linked acro-gigantism syndrome