A Case Report of Shwachman-Diamond Syndrome Caused by Heterozygous Variants in the EFL1 Gene and Literature Review.

OBJECTIVE

This investigation reports on a Shwachman-Diamond syndrome (SDS) case arising from compound heterozygous genetic variations affecting the EFL1 locus. A systematic review of published literature was undertaken to compile data on clinical manifestations, management strategies, and prognostic indicators in SDS cases with identified EFL1 genetic alterations.

METHODS

The clinical data of a neonatal SDS patient, whole exome sequencing (WES) results, and the pathogenicity of the variants were analyzed. A comprehensive survey of applicable medical literature published up to March 2025 was executed to identify and synthesize the clinical phenotypes associated with this condition.

RESULTS

WES identified compound heterozygous variants within the patient's EFL1 gene: c.2935C>T (p.R979C) and c.3149_3151delCAC (p.P1050del). Bioinformatics analysis indicated these variations were damaging. Seven articles reported a total of 20 cases of this disease, with predominant phenotypes including exocrine pancreatic insufficiency, hematologic abnormalities, and metaphyseal dysplasia. Among the 20 previously reported cases, 16 distinct EFL1 variants were identified, and the current case adds 2 novel variants.

CONCLUSION

SDS caused by EFL1 gene defects primarily presents as bone marrow failure, with treatment mainly focused on symptomatic management. We report a neonatal SDS patient with the earliest onset of symptoms. The c.2935C>T and c.3149_3151delCAC compound heterozygous variants reported in this study expand the mutational spectrum of this disease.