Retrospective evaluation of the phenotypic-genotypic characteristics of patients with short stature who underwent next-generation sequencing analysis

Rabia Meral; en Er; Filibeli Berna Eroğlu; Ozgur Kırbıyık; Guvenc Merve Saka; Dundar Bumin Nuri

doi:10.1530/endoabs.110.P587

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Endocrine Abstracts (2025) 110 P587 | DOI: 10.1530/endoabs.110.P587

ECEESPE2025 Poster Presentations Growth Axis and Syndromes (91 abstracts)

Retrospective evaluation of the phenotypic-genotypic characteristics of patients with short stature who underwent next-generation sequencing analysis

Rabia Meral ¹ , Eren Er ² , Berna Eroğlu Filibeli ² , Özgür Kırbıyık ³ , Merve Saka Güvenç ³ & Bumin Nuri Dündar ⁴

Author affiliations

¹Kahramanmaraş Necip Fazıl City Hospital, Pediatric Endocrinology Clinic, Kahramanmaraş, Türkiye; ²Izmir City Hospital, Pediatric Endocrinology Clinic, Izmir, Türkiye; ³İzmir City Hospital, Genetic Diseases Diagnostic Center, Izmir, Türkiye; ⁴Izmir Katip Celebi University, Faculty of Medicine, Department of Pediatric Endocrinology, Izmir, Türkiye

JOINT2411

Background: Short stature is a common pediatric endocrinological disorder with an incidence of 3-5%. The majority of cases have an unclear etiology, which complicates therapy selection and the diagnostic process.

Objective: This study aims to explore the phenotypic-genotypic relationships by retrospectively evaluated patients who underwent targeted next-generation sequencing (NGS) due to short stature.

Materials and Methods: This study included 65 patients (37 male, 28 female) who were followed up for short stature [< -2 SDS (standard deviation score)] between January 2011 and June 2022 at Pediatric Endocrinology Clinic and underwent targeted NGS. The pathogenicity of the variants was evaluated according to the criteria of the American College of Medical Genetics and Genomics (ACMG). Patients with pathogenic or likely pathogenic variants detected in the NGS panel (Group 1) were compared with other patients included in the study (Group 2) in terms of their characteristics.

Results: The mean age at diagnosis of the patients was 7. 93±4. 42 years (min; max: 0. 42; 15. 78), and the mean height SDS was -3. 06±0. 97 (min; max: -7. 37; -2. 00). Among the patients, 15 (23. 1%) had consanguinity between their parents. Forty participants (61. 5%) had at least one individual with short stature in their family. The number of patients with pathogenic or likely pathogenic variants detected in the NGS panel was 19 (29. 2%). These variants were FLNB (3 patients), OBSL1 (2 patients), FBN1, EXT1, ADAMTSL4, PHEX, LHX3, FLNB, ROR2, ALPL, TTC21B, GHR, SLC26A2, PCNT, NF1, FGFR3, GHRHR. The birth weight SDS of patients in Group 1 was statistically lower than that of patients in Group 2 (−1. 69±1. 7 vs. −0. 56±1. 08, P = 0. 046). The rate of consanguinity among the parents of patients in Group 1 was 47. 2%, whereas it was 13. 0% in Group 2, and this difference was statistically significant (P = 0. 007).

Conclusion: In this study, NGS panel screening was used to determine the genetic etiology of short stature in some patients and provided a solid informational basis for clinical phenotype classification and genetic counseling. Additionally, genetic screening can provide a foundation for the development of more effective interventions and help meet the medical needs. Further functional experimental research is required on variants of potential pathogenic significance.