ShwachmanDiamondSyndrom

Shwachman-Diamond syndrome, often abbreviated SDS, is a rare inherited bone marrow failure syndrome characterized by exocrine pancreatic insufficiency, skeletal abnormalities, and variable hematologic manifestations. It is caused by biallelic pathogenic variants in the SBDS gene and is inherited in an autosomal recessive manner.

Clinical features typically present in infancy or early childhood. Exocrine pancreatic insufficiency leads to malabsorption and poor weight gain, frequently requiring pancreatic enzyme replacement therapy and nutritional support. Skeletal abnormalities can include metaphyseal dysostosis and thoracic cage anomalies, contributing to short stature and characteristic radiographic findings. Hematologic issues are common and range from chronic neutropenia to anemia or occasional thrombocytopenia, and patients may have increased susceptibility to infections. Immunologic defects may be present, further elevating infection risk. Some individuals develop bone marrow failure or, later, clonal evolution to myelodysplastic syndrome or acute myeloid leukemia.

Diagnosis is based on a combination of clinical features and confirmatory genetic testing. A high index of suspicion arises in a child with pancreatic insufficiency, growth delay, skeletal anomalies, and hematologic abnormalities. Laboratory studies often show neutropenia and may reveal anemia or other cytopenias; fecal elastase is typically reduced. Definitive diagnosis is established by detecting biallelic SBDS mutations. Bone marrow examination can reveal hypocellularity with dysplastic changes, but findings are not specific.

Management is multidisciplinary and supportive. Pancreatic enzyme replacement and nutrition management address malabsorption. Infections are treated per standard guidelines, and hematologic issues may be managed with growth factors like G-CSF in selected cases. Hematopoietic stem cell transplantation is considered for severe marrow failure or malignant transformation. Regular monitoring of growth, nutrition, hematologic status, and cancer risk is recommended. The condition is named after Shwachman and Diamond, who first described it in 1964.