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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Clinical and genetic diagnosis and management of Silver-Russell syndrome: Report of four cases
Ilektra Toulia, Parthena Savvidou, Athina Ververi, Maria G Grammatikopoulou, Konstantina Kosta, Vaya Tziaferi, Charalampos Antachopoulos, Dimitrios G Goulis, Alexandros Sotiriadis, Kyriaki Tsiroukidou
Ilektra Toulia, Parthena Savvidou, Konstantina Kosta, Kyriaki Tsiroukidou, Endocrine Unit, 3rd Pediatric Department, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Kentrikí Makedonía, Greece
Athina Ververi, Department of Genetics for Rare Diseases, Papageorgiou General Hospital, Thessaloniki GR-54124, Kentrikí Makedonía, Greece
Maria G Grammatikopoulou, Immunonutrition Unit, Department of Rheumatology & Clinical Immunology, University of Thessaly, Larissa University Hospital, Larissa GR-41223, Thessalía, Greece
Vaya Tziaferi, Pediatric Endocrinology Clinic, Thessaloniki GR-55535, Kentrikí Makedonía, Greece
Charalampos Antachopoulos, 3rd Department of Pediatrics, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki GR-54124, Kentrikí Makedonía, Greece
Dimitrios G Goulis, First Department of Obstetrics and Gynecology, Medical School, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Thessaloniki GR-54601, Kentrikí Makedonía, Greece
Alexandros Sotiriadis, 2nd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki GR-54124, Greece
Co-first authors: Ilektra Toulia and Parthena Savvidou.
Co-corresponding authors: Maria G Grammatikopoulou and Alexandros Sotiriadis.
Author contributions: Toulia I, Savvidou P, Kosta K, and Tziaferi V collected the data; Toulia I and Savvidou P contributed equally to this work as co-first authors; Ververi A contributed to the genetic analyses; Antachopoulos C, Goulis DG, and Sotiriadis A supervised the process; Tsiroukidou K contributed to conceptualization and supervision; Toulia I, Savvidou P, Grammatikopoulou MG, Antachopoulos C, Goulis DG, Sotiriadis A, and Tsiroukidou K wrote the manuscript; Grammatikopoulou MG and Sotiriadis A contributed equally to this work as co-corresponding authors; and all authors edited, read, and approved the final manuscript.
Informed consent statement: All study participants or their legal guardians provided informed written consent for the publication of this case report.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Maria G Grammatikopoulou, PhD, Assistant Professor, Immunonutrition Unit, Department of Rheumatology & Clinical Immunology, University of Thessaly, Larissa University Hospital, Argonafton & Filellinon Street, Larissa GR-41223, Thessalía, Greece.
mgrammat@uth.gr
Received: August 13, 2024
Revised: November 19, 2024
Accepted: January 7, 2025
Published online: June 9, 2025
Processing time: 216 Days and 10.3 Hours
BACKGROUND
Silver-Russell syndrome (SRS) is a clinically heterogeneous entity characterized by intrauterine and postnatal growth restriction, relative macrocephaly at birth, distinct facial features, and body asymmetry combined with other malformations.
CASE SUMMARY
Herein, we describe four individuals with SRS, focusing on their prenatal phenotype, postnatal presentation, diagnosis, and management. All cases had a typical phenotype, including postnatal growth failure, short stature (chronic malnutrition), and protruding forehead. Individually, they presented with feeding difficulties, leg length discrepancy, triangular face, or relative macrocephaly at birth, and each one exhibited distinct SRS features, including motor and/or speech delay, experiencing frequent hypoglycemic episodes. The fact that each patient exhibited a different combination of clinical findings underlines the heterogeneity of the syndrome.
CONCLUSION
SRS is diagnosed clinically. However, only 60% of cases are genetically confirmed, while most are sporadic. Although SRS is a well-described syndrome, a delayed diagnosis can have grave consequences on a child’s growth. Recombinant human growth hormone treatment is often initiated shortly after the diagnosis. The follow-up requires a multidisciplinary approach.
Core Tip: The present case series questions whether premature delivery should be induced in fetal growth restriction fetuses with the Silver-Russell syndrome (SRS) genotype as it further aggravates growth. The manifestation of SRS symptoms varies greatly in each patient. When premature delivery is induced due to fetal growth restriction, these newborns carry the double burden of SRS and prematurity, making it more difficult for them to catch up with growth and develop properly.
