Contribution of Dynamic and Genetic Tests for Short Stature Diagnosing: A Case Report

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.

Automated summary

This report describes a case of short stature in an adult patient with homozygous variants in the ADAMTS17 and GHS-R genes. The patient exhibited severe short stature, small hands and feet, and eye disturbances. Genetic testing revealed compound homozygosity for ADAMTS17, responsible for Weill-Marchesani-like syndrome, as well as homozygous variants in the GHS-R gene. Dynamic stimulation tests showed a normal GH response to insulin tolerance test but a flattened response to macimorelin stimulus. The findings provide insights into the clinical spectrum, associated co-morbidities, implications in dynamic tests, genetic counseling, and treatment options for both the index case and her relatives.