Shwachman syndrome

Shwachman-Diamond syndrome (SDS) is a rare congenital disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal abnormalities, and short stature. After cystic fibrosis (CF), it is the second most common cause of exocrine pancreatic insufficiency in children. more...

Clinical Features

This syndrome shows a wide range of abnormalities and symptoms. The main characteristics of the syndrome are exocrine pancreatic dysfunction, haematologic abnormalities and growth retardation. Neutropenia may be intermittent or persistent and is the most common haematological finding. Low neutrophil counts leave patients at risk of developing severe recurrent infections that may be life-threatening. Anemia (low red blood cell counts) and thrombocytopenia (low platelet counts) may also occur. Bone marrow is typically hypocellular, with maturation arrest in the myeloid lineages that give rise to neutrophils, macrophages, platelets and red blood cells. Patients may also develop progressive marrow failure or transform to acute myelogenous leukemia. Pancreatic exocrine insufficiency arises due to a lack of acinar cells that produce digestive enzymes. These are extensively depleted and replaced by fat. A lack of pancreatic digestive enzymes leaves patients unable to digest and absorb fat. However, pancreatic status may improve with age in some patients. More than 50% of patients are below the third percentile for height, and short stature appears to be unrelated to nutritional status. Other skeletal abnormalities include metaphyseal dysostosis (45% of patients), thoracic dystrophy (rib cage abnormalities in 46% of patients), and costochondral thickening (shortened ribs with flared ends in 32% of patients). Skeletal problems are one of the most variable components of SDS, with 50% affected siblings from the same family discordant for clinical presentation or type of abnormality. Despite this, a careful review of radiographs from 15 patients indicated that all of them had at least one skeletal anomaly, though many were sub-clinical.

Diagnosis

Initially, the clinical presentation of SDS may appear similar to cystic fibrosis. However, CF can be excluded with a normal sweat chloride test result. The variation, intermittent nature, and potential for long-term improvement of some clinical features make this syndrome difficult to diagnose. SDS may present with either malabsorption, or hematological problems. Rarely, SDS may present with skeletal defects, including severe rib cage abnormalities that lead to difficulty in breathing. Diagnosis is generally based on evidence of exocrine pancreatic dysfunction and neutropenia. Skeletal abnormalities and short stature are characteristics that can be used to support the diagnosis. The gene responsible for the disease has been identified and genetic testing is now available. Though useful in diagnostics, a genetic test does not surmount the need for careful clinical assessment and monitoring of all patients.

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