Clinical Spectrum and Molecular Pathophysiology of Shwachman-Diamond Syndrome

Shwachman-Diamond Syndrome (SDS) is an inherited marrow failure syndrome associated with exocrine pancreatic dysfunction and leukemia predisposition. SDS patients may also manifest additional non-hematologic abnormalities. Autosomal recessive mutations in the SBDS gene are found in over 90 percent of patients fitting the classical clinical phenotype of SDS. The advent of genetic testing has revealed an unexpectedly broad range of SDS phenotypes. Through the Shwachman-Diamond Syndrome Registry, we found that diagnosis may be obscured by cryptic or non-classical presentations of SDS. The timely diagnosis of SDS carries profound ramifications for medical management and treatment. We are developing assays utilizing massively parallel next generation sequencing to address this challenging diagnostic problem. Clinical applications of next generation sequencing to the diagnostic algorithm for marrow failure or myelodysplastic syndrome and implications for medical treatment will be explored.