Contribution of Dynamic and Genetic Tests for Short Stature Diagnosing: A Case Report
Betina Biagetti,
Irene Valenzuela,
Ariadna Campos-Martorell,
Berta Campos,
Sara Hernandez,
Marina Giralt,
Noelia Díaz-Troyano,
Emilio Iniesta-Serrano,
Diego Yeste,
Rafael Simó
Affiliations
Betina Biagetti
Endocrinology Department, Diabetes and Metabolism Research Unit, Vall d’Hebron University Hospital and Vall d’Hebron Research Institute (VHIR), Universidad Autónoma de Barcelona, Reference Networks (ERN), 08035 Barcelona, Spain
Irene Valenzuela
Department of Clinical and Molecular Genetics and Rare Disease Unit and Medicine Genetics Group, Vall Hebron Research Institute, 08035 Barcelona, Spain
Ariadna Campos-Martorell
Pediatric Endocrinology Section, Vall d’Hebron University Hospital and Vall d’Hebron Research Institute (VHIR), Universidad Autónoma de Barcelona, 08193 Barcelona, Spain
Berta Campos
Department of Clinical and Molecular Genetics and Rare Disease Unit and Medicine Genetics Group, Vall Hebron Research Institute, 08035 Barcelona, Spain
Sara Hernandez
Pediatric Endocrinology Section, Vall d’Hebron University Hospital and Vall d’Hebron Research Institute (VHIR), Universidad Autónoma de Barcelona, 08193 Barcelona, Spain
Marina Giralt
Department of Biochemistry, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
Noelia Díaz-Troyano
Department of Biochemistry, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
Emilio Iniesta-Serrano
Pharmacy Department, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
Diego Yeste
Pediatric Endocrinology Section, Vall d’Hebron University Hospital and Vall d’Hebron Research Institute (VHIR), Universidad Autónoma de Barcelona, 08193 Barcelona, Spain
Rafael Simó
Endocrinology Department, Diabetes and Metabolism Research Unit, Vall d’Hebron University Hospital and Vall d’Hebron Research Institute (VHIR), Universidad Autónoma de Barcelona, Reference Networks (ERN), 08035 Barcelona, Spain
Genetic tests have led to the discovery of many novel genetic variants related to growth failure, but the clinical significance of some results is not always easy to establish. The aim of this report is to describe both clinical phenotype and genetic characteristics in an adult patient with short stature associated with a homozygous variant in disintegrin and metalloproteinase with thrombospondin motifs type 17 gene (ADAMTS17) combined with a homozygous variant in the GH secretagogue receptor (GHS-R). The index case had severe short stature (SS) (−3.0 SD), small hands and feet, associated with eye disturbances. Genetic tests revealed homozygous compounds for ADAMTS17 responsible for Weill–Marchesani-like syndrome but a homozygous variant in GHS-R was also detected. Dynamic stimulation with an insulin tolerance test showed a normal elevation of GH, while the GH response to macimorelin stimulus was totally flattened. We show the implication of the GHS-R variant and review the molecular mechanisms of both entities. These results allowed us to better interpret the phenotypic spectrum, associated co-morbidities, its implications in dynamic tests, genetic counselling and treatment options not only to the index case but also for her relatives.
