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. 2025 Dec 10;13(12):e70440.
doi: 10.1002/rcr2.70440. eCollection 2025 Dec.

Beyond Cystic Fibrosis: Recognising Shwachman-Diamond Syndrome in the Respiratory Clinic

Freda Yang  1   2 , Ladina Weitnauer  3 , Imogen Felton  1   3 , Nicholas J Simmonds  1   3
Affiliations

Beyond Cystic Fibrosis: Recognising Shwachman-Diamond Syndrome in the Respiratory Clinic

Freda Yang et al. Respirol Case Rep. .

Abstract

Cystic fibrosis (CF) and Shwachman-Diamond Syndrome (SDS) share overlapping features, including recurrent respiratory infections and pancreatic insufficiency, which can complicate diagnosis. We report a case of a six-year-old girl who presented with productive cough, steatorrhea and recurrent infections. Initial evaluation showed abnormal liver enzymes, elevated immunoreactive trypsin, neutrophil dysfunction and skeletal anomalies. Sweat test was equivocal and CFTR genetic panel was negative. Further genomic analysis identified compound heterozygous mutations in the SBDS gene: c.258+2T>C (known pathogenic variant) and c.284T>A (novel variant), confirming SDS. Over a 42-year follow-up, she experienced intermittent neutropenia, recurrent respiratory infections and pregnancy-related complications. This case emphasises the importance of considering SDS in CF-like presentations with atypical features and equivocal CF testing. Milder SDS phenotypes can survive into adulthood. Further work is needed to refine genotype-phenotype correlations and guide long-term management.

Keywords: CFTR; SDBS; Shwachman‐Diamond Syndrome; cystic fibrosis.

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Conflict of interest statement

F.Y. has received honoraria for attending meetings and speaker fees from AstraZeneca and GlaxoSmithKline, and is a member of the BTS asthma specialist advisory group. L.W. has no conflicts of interest; I.F. has received honoraria for educational symposia by Vertex. N.J.S. has received honoraria for advisory boards from Vertex, Boehringer Ingelheim, Chiesi, Gilead, and Menarini. He has also received honoraria for educational activities from Vertex, Chiesi, Gilead, Medison, Teva, and Zambon.

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