Evaluation of Cytogenetic and Molecular Genetic Tests in Patients with Short Stature

Short stature is among the most common endocrinological diseases in childhood. The investigation of syndromic or non-syndromic genetic causes provides important data for etiology. This study aimed to present the frequency of genetic variant detection in cases in which genetic studies were performed for short stature in our clinic and the clinical characteristics of patients in whom clinically significant variants were detected.

Two hundred forty-six patients who applied to our center with complaints of short stature and underwent genetic testing during a 1.5-year period were included. Anthropometric measurements, history and physical examination findings, and tests for the etiology of short stature were recorded retrospectively for all patients with pathological results.

Genetic tests were performed for a total of 228 children with short stature, of whom 39 (17.2%) were male and 189 (82.8%) were female. Pathogenic variants were identified in 56 (24.5%) of 228 patients. The mean height standard deviation score (SDS) of all patients was -2.63 ± 1.42. The height SDS of the patients with the gene variant was -2.73 ± 1.32. Pathological results were detected in 26 of 113 patients (23%) who underwent karyotype analysis, while clinically significant pathogenic results were obtained in 2 of 67 patients (2.9%) who underwent microarray analysis, 9 of 76 patients (30.8%) who underwent short stature panel analysis, 5 of 18 patients (27.7%) who underwent RASopathy panel testing, 7 of 37 patients (15%) who underwent SHOX MLPA, and 7 of 17 patients (6.9%) who underwent skeletal dysplasia panel analysis.

Different genetic causes and pathophysiological processes underlie isolated and/or syndromic short stature. With the development in genetics, it is becoming easier and more important to elucidate the etiology of short stature, as in other diseases. Our study supports the significance of genetic diagnosis in patients with short stature, as it can enable diagnosis even in the absence of specific clinical findings other than short stature, and guide the necessity, efficacy, and appropriate dosing of growth hormone therapy.