Shwachman-Diamond syndrome (SDS, also known as Shwachman-Diamond-Oski syndrome) generally presents in infancy with exocrine pancreatic dysfunction and bone marrow failure. Since its initial description in the early 1960s [1-3], clinical features associated with SDS have been identified. In addition, advances in molecular genetics have established that SDS is an autosomal recessive disorder.
The genetic abnormalities, clinical manifestations, diagnosis, and management of Shwachman-Diamond syndrome will be reviewed here.
Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder. In approximately 90 percent of affected patients who have been studied, mutations have been detected in the Shwachman-Bodian-Diamond syndrome (SBDS) gene located on chromosome 7q11 [4,5]. The SBDS gene has an adjacent pseudogene (a nonfunctional but almost identical gene) and, in the majority of cases, gene conversion mutations recombine portions of the pseudogene and SBDS gene, resulting in a dysfunctional SBDS gene . At the present time, there is no known correlation between identified mutations and severity of disease .
The SBDS gene is highly conserved throughout evolution and is expressed in all human tissues tested to date [5,7,8]. The SBDS protein has been implicated in ribosome biogenesis and mitotic spindle stabilization [5,7-13]. Using human and animal models, investigators have shown that the SBDS gene product has an important role in the maturation of the 60S ribosomal subunit and ribosome assembly [14-18]. How this defect in ribosomal function leads to the clinical manifestations of SDS has not been established. One hypothesis is that the high protein secretory capacity of neutrophils, pancreatic acinar cells, and chondrocytes makes them particularly vulnerable to defects in ribosomal assembly . SBDS protein colocalizes with the mitotic spindle and binds to and stabilizes purified microtubules [11,20]. It is currently unclear which functions of SBDS contribute to marrow failure.
In a mouse model, homozygous expression of SBDS gene mutations leads to early fetal death  consistent with an essential role for SBDS in early mammalian development.