Clinical characteristics and genetic mutation analysis in 18 pediatric patients with Shwachman-Diamond syndrome

Ruoying Wei; Kaihui Zhang; Chen Liu; Xuxia Wei; Qin Jiang; Ji-An Li; Meiling Huo; Yinggang Liu; Mohnad Abdalla; Li-An Du; Xiaomei Yang; Fu Li

doi:10.3389/fgene.2025.1603782

Clinical characteristics and genetic mutation analysis in 18 pediatric patients with Shwachman-Diamond syndrome

Front Genet. 2025 Jun 18:16:1603782. doi: 10.3389/fgene.2025.1603782. eCollection 2025.

Authors

Ruoying Wei¹, Kaihui Zhang², Chen Liu³, Xuxia Wei⁴, Qin Jiang⁵, Ji-An Li⁶, Meiling Huo⁷, Yinggang Liu⁸, Mohnad Abdalla², Li-An Du¹, Xiaomei Yang¹, Fu Li¹

Affiliations

¹ Hematology and Oncology Department, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China.
² Pediatric Research Institute, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China.
³ Neonatology Department, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China.
⁴ Gastroenterology Department, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China.
⁵ Critical Care Medicine Department, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China.
⁶ Infectious Diseases Department, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China.
⁷ Endocrinology Department, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China.
⁸ Beijing Mygenostics Medical Laboratory, Beijing, China.

Abstract

Purpose: To investigate the clinical features and genetic mutation spectrum of 18 children with Shwachman-Diamond syndrome (SDS).

Methods: Data from 18 children with SDS at Shandong University Affiliated Children's Hospital (Ji'nan Children's Hospital) between April 2016 and June 2024 were retrospectively analyzed. Variant sites were confirmed by Sanger sequencing in family lines.

Results: Patients exhibited complex and diverse clinical symptoms, often involving multiple systems. The clinical features of this cohort included (1) early onset (median age: 1.5 months), diarrhea, trypsin reduction, neutropenia, and growth retardation and (2) high incidence of pancreatic imaging abnormalities, bone marrow hypoplasia, developmental malformations, and neurocognitive disorders. All patients had homozygous or compound heterozygous SBDS mutations, with 258+2T>C identified as the hotspot mutation (20/37), while 41A>T and 185A>C were newly discovered mutations.

Conclusion: Patients with SDS exhibit clinical heterogeneity, and this study enriches the SBDS gene mutation spectrum. Genetic testing is valuable for early diagnosis.

Keywords: SBDS gene; Shwachman-Diamond syndrome; bone marrow failure disorders; child; myelodysplastic syndrome.