Shwachman-Diamond syndrome: clinical phenotypes.

The clinical phenotype of Shwachman-Diamond syndrome (SDS) is extremely heterogeneous, showing a wide range of abnormalities and symptoms. The main characteristics of the syndrome are exocrine pancreatic dysfunction, haematologic abnormality and growth retardation. At diagnosis, especially when made in infancy, symptoms of pancreatic insufficiency are always present. This condition could be considered as a transient pancreatic insufficiency. In fact, several studies have shown that, with advancing age, about 40-60% of patients become pancreatic sufficient. Observations on the evolution of pancreatic activity lead us to believe that the diagnosis of SDS must be considered even in the absence of signs and symptoms of pancreatic insufficiency. Intermittent neutropenia is the most common haematological finding in SDS, but more of the bone marrow cellular elements can be involved. In recent years, recombinant human granulocyte colony-stimulating factor has been used in some SDS subjects with severe neutropenia and frequent infection. The major haematological problem in the disease is the appearance of acute myeloid leukaemia; however, its prevalence is difficult to establish. Growth retardation is a typical manifestation. Weight and length are deficient at birth and remain below normal over time. Some studies show that SDS patients present short stature rather than malnutrition and this would suggest an inherent growth problem. A broad spectrum of skeletal abnormalities has been found to be associated with this syndrome. Short ribs with broadened anterior ends and metaphyseal dyschondroplasia of the long bone are the most common findings. Elevated liver enzymes and hepatomegaly are present in the first years of life with subsequent improvement without complications. Developmental delay, learning disorders and attention deficit disorders are also reported.