gigantism; pituitary tumor; GPR101; topologically associating domain (TAD); somatostatin analog
Abstract :
[en] X-linked acrogigantism (X-LAG) is a rare form of pituitary gigantism that is associated with growth hormone (GH) and prolactin-secreting pituitary adenomas/pituitary neuroendocrine tumors (PitNETs) that develop in infancy. It is caused by a duplication on chromosome Xq26.3 that leads to the misexpression of the gene GPR101, a constitutively active stimulator of pituitary GH and prolactin secretion. GPR101 normally exists within its own topologically associating domain (TAD) and is insulated from surrounding regulatory elements. X-LAG is a TADopathy in which the duplication disrupts a conserved TAD border, leading to a neo-TAD in which ectopic enhancers drive GPR101 over-expression, thus causing gigantism. Here we trace the full diagnostic and therapeutic pathway of a female patient with X-LAG from 4Cseq studies demonstrating the neo-TAD through medical and surgical interventions and detailed tumor histopathology. The complex nature of treating young children with X-LAG is illustrated, including the achievement of hormonal control using a combination of neurosurgery and adult doses of firstgeneration somatostatin analogs.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Caruso, Manuela; Department of Pediatrics, Azienda Policlinico Università di Catania, Italy
Mazzatenta, Diego; Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum, University of Bologna, Bologna, Italy ; Istituto di Ricovero e Cura a Carattere Scientifico Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
Asioli, Sofia; Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum, University of Bologna, Bologna, Italy ; Istituto di Ricovero e Cura a Carattere Scientifico Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
Costanza, Giuseppe; Department of Pediatrics, Azienda Policlinico Università di Catania, Italy
Trivellin, Giampaolo; Department of Biomedical Sciences, Humanitas University, Milan, Italy ; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Milan, Italy
Franke, Martin; Andalusian Center for Developmental Biology (CABD), Universidad Pablo de Olavide (UPO) -Consejo Superior de Investigaciones Cientificas (CSIC), Sevilla, Spain
Abboud, Dayana ; Université de Liège - ULiège > GIGA > GIGA Molecular Biology of Diseases - Molecular Pharmacology
Hanson, Julien ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Veronique Raverot; Laboratoire d'hormonologie Centre de Biologie et Pathologie Est (CBPE)-Groupement Hospitalier Est, Hospices civils de Lyon, Bron, France
Pétrossians, Patrick ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Beckers, Albert ; Université de Liège - ULiège > Département des sciences cliniques
Cappa, Marco; Innovative Therapies for Endocrinopathies, Scientific Directorate, Research Unit, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
Daly, Adrian ; Université de Liège - ULiège > Département des sciences cliniques
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