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

Area of Science:

• Medical Genetics
• Pediatric Pulmonology
• Hematology

Background:

• Cystic fibrosis (CF) and Shwachman-Diamond Syndrome (SDS) present with overlapping clinical features, such as respiratory and pancreatic dysfunction.
• Diagnostic challenges arise due to similar symptoms, necessitating advanced genetic testing for accurate differentiation.

Purpose of the Study:

• To report a case of a pediatric patient with CF-like symptoms.
• To highlight the diagnostic utility of genomic analysis in identifying SDS.
• To emphasize the importance of considering SDS in atypical CF presentations.

Main Methods:

• Case report of a six-year-old girl with productive cough, steatorrhea, and recurrent infections.
• Initial investigations included liver function tests, immunoreactive trypsin, neutrophil function assays, and skeletal imaging.
• Sweat testing and CFTR genetic panel were performed, followed by SBDS gene sequencing for genomic analysis.

Main Results:

• Genomic analysis revealed compound heterozygous mutations in the SBDS gene (c.258+2T>C and c.284T>A), confirming a diagnosis of Shwachman-Diamond Syndrome.
• The patient experienced a 42-year follow-up with intermittent neutropenia, recurrent respiratory infections, and pregnancy complications.
• The novel c.284T>A variant was identified alongside a known pathogenic variant.

Conclusions:

• This case underscores the critical role of SBDS gene analysis in diagnosing SDS, especially in patients with CF-like presentations and equivocal CF testing.
• Milder SDS phenotypes allow for survival into adulthood, with long-term management challenges.
• Further research is required to establish precise genotype-phenotype correlations for improved management strategies.