SAT-197 Clinical and genetic investigation in children with short stature and comparison of effectiveness of growth hormone therapy

Abstract Disclosure: G. Kim: None. J. Yu: None. Objective: Growth hormone stimulation tests (GHST) have been performed to identify growth hormone deficiency (GHD) as a cause of short stature (SS). With the advancement of genetic testing techniques, the use of next-generation sequencing (NGS) panels has increased. This study aimed to analyze factors related to the diagnosis and treatment of GHD and NGS results in children with SS. Subjects and Methods: The study included patients with short stature who underwent both NGS panel testing and GHST at our Hospital between July 2020 and December 2024. Data were collected retrospectively based on the medical records, including age, sex, height, weight, bone age, IGF-1 levels during GHST and follow-up periods as well as NGS results. Statistical analyses were conducted using cross-tabulation, Pearson’s chi-square test, and Fisher’s exact test. Results: A total of 59 children who underwent NGS panel testing and GHST were included in the study cohort. The male-to-female ratio was 0.98:1.02. The mean age at the time of GHST was 6.1 years. GHD was diagnosed when all GH peak levels were below 10 ng/mL during 2 or more GHST. Insulin, arginine, glucagon, or L-dopa have been used as the pharmacologic stimulants in GHST. Twenty patients (33.9%) were diagnosed with GHD. Thirteen (65%) were males in GHD group, while 16 (41%) were males in idiopathic short stature (ISS) group. Male was significantly higher in the GHD group (P<0.05). Other factors such as age at GHST, GH peak levels, height, weight, and IGF-1 levels at GHST showed no significant differences between the GHD and ISS groups. Those factors also showed no significant differences at the time of recent FU. The NGS panel initially included 30 essential genes until July 2022, after which the panel expanded to 68 essential genes. Positive NGS results were defined as pathogenic variants (PV) or likely pathogenic variants (LPV). Genes classified as positive included PTPN11, NF1, GREB1L, OBSL1, COG4, and ACAN. Genes classified as variant of uncertain significance (VUS) included 37 genes including CUL7, PCNT, ACAN, GLI2, INTS1, KMT2D, and OBSL1. Among the positive results, PTPN11 was identified in 4 patients, with 1 (25%) diagnosed with GHD. Among the VUS, CUL7 and PCNT were the most common, each found in 6 patients, followed by ACAN, GLI2, INTS1, KMT2D, and OBSL1. Conclusion: This cohort also showed a significantly higher proportion of males in the GHD group. However, other factors, such as height, weight, and IGF-1 levels during GHST, showed no significant differences in the mean value between the GHD and ISS groups, suggesting that GHD and ISS can be explained as the single disease spectrum. Although this study had limitations due to its small sample size, it showed that syndromic short stature was more common than defects in the GH signaling pathway in children with SS. Presentation: Saturday, July 12, 2025