Shwachman-Diamond syndrome is marked by the association of an haematological defect with a dysmorphic syndrome characterised by lipomatosis of the pancreas resulting in external pancreatic insufficiency. This disease is very rare, with no more than a hundred cases reported in France. Other clinical signs include cutaneous effects (ichtyosis), bone defects (metaphyseal dysostosis, pectus carinatum), and psychomotor retardation. Magnetic resonance imaging (MRI) reveals a typical hyposignal in T2. Neutropaenia with deficient chemotaxis together with moderate thrombopaenia and anaemia and increased levels of foetal haemoglobulin have also been noted. This central haematological disturbance worsens and evolves towards aplasia in 25% of cases. Despite some similarities with Pearson syndrome, Shwachman-Diamond disease cannot be explained by mitochondrial DNA defects. Mutations occurring in the ubiquitous SBDS gene, located on chromosome 7, are found in most patients. The functions of the causative gene are highly polymorphic, making it difficult to explain the complex clinical picture. As long as neutropaenia is moderate and asymptomatic, patient management should be nutritional (pancreatic enzyme, nutritional and vitamin support). Hematopoietic growth factor (granulocyte colony-stimulating factor, G-CSF) therapy is sometimes beneficial. Patients affected by this syndrome are at increased risk of secondary leukaemia (principally acute myeloblastic leukaemia type FAB 5 or 6) or a myelodysplastic syndrome with cytological abnormalities (in particular, clonal cytological abnormalities frequently affecting chromosome 7). In cases where the disease evolves towards medular aplasia or malignant transformation, bone marrow transplant is required.
Last update: February 2005