ESPE Abstracts (2022) 95 P1-517

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1Istanbul University, Istanbul Faculty of Medicine, Department of Paediatrics, Paediatric Endocrinology Unit, Istanbul, Turkey; 2Istanbul University, Istanbul Faculty of Medicine, Department of Medical Genetics, Istanbul, Turkey


Background: Approximately 10-15% of small for gestational age (SGA) newborns are at risk of having subnormal growth and persistent short stature. It is postulated that a large amount of persistent short stature results from genetic abnormalities, which are commonly characterized by dysmorphic features and developmental disorders.

Aim: To uncover the genetic etiology of syndromic short stature children born SGA.

Methods: We recruited 50 patients born SGA with syndromic short stature. Candidate gene analysis/fluorescence in situ hybridization (FISH)/methylation-specific multiplex ligation dependent probe amplification (MS-MLPA) was performed in children with a clinical suspicion for a specific genetic syndrome based on clinical and laboratory studies. Clinically undiagnosed cases and children with negative results using candidate gene approach underwent chromosomal microarray analysis (CMA). Children with negative results with the above analyses are enrolled for whole-exome sequencing analysis (WES).

Results: Of 22 patients with clinical suspicion of a recognized syndrome, 15 had positive results. Three patients were diagnosed with Silver-Russel syndrome using MS-MLPA and one with Williams-Beuren Syndrome by FISH technique. Pathogenic/likely pathogenic variants found in candidate gene analysis were as follows: OBSL1 (n=4), CUL7 (n=3), COL1A2, CREBBP, NPR2, and GNAS (n=1 each). Two pathogenic copy number variants associated with short stature were detected with CMA in the remaining 35 patients, namely 7p22 microduplication syndrome and 1q21.1 duplication syndrome. With this diagnostic algorithm, 17 (34%) patients had a definitive diagnosis.

Conclusion: Further genetic analyses may provide a definitive diagnosis in syndromic SGA with persistent short stature. Preliminary results of this study allowed us to improve the clinical management and present a clear explanation to families regarding the disease.

Keywords: Short stature, Small for gestational age, Syndrome, Genes and growth, Genetic etiology

Acknowledgements: This work was supported by Scientific Research Projects Coordination Unit of Istanbul University. Project number: TYO-2022-38111

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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