Shwachman-Diamond-Bodian Syndrome (SBDS): Long-Term Follow-Up of 31 Patients.

Shwachman-Bodian-Diamond syndrome (SBDS) is an autosomal recessive multisystem disorder primarily affecting the bone marrow, exocrine pancreas, and skeleton. As with other constitutional bone marrow failure syndromes, there is a predisposition to malignant myeloid transformation. The risk can only be estimated and varies considerably in the literature. Significant hematologic abnormalities can be present from early childhood with requirement of growth factor treatment (granulocyte-colony stimulating factor, erythropoietin). Since the first description of mutations in the SBDS gene, most clinically diagnosed patients have been genetically analyzed meanwhile, which now allows for genotype-phenotype correlations. Here, we report long-term clinical data of 31 SBDS patients (10 female, 21 male; 27 patients alive, 3 expired, 1 lost to follow up) with regard to different genotypes collected by the European Branch of the Severe Chronic Neutropenia International Registry since 1994: Severe Neutropenia (ANC CT/258+2T>C. The rare genotypes 199A>G/258+2T>C, 297–300delAAGA/258+2T>C, and TGC>TGG/258+2T>C were observed in single patients. In another individual, a complex aberration with 7 mutations (Rosendahl et al, 2006) was found. Interestingly, two of the latter four patients presented with severe hematological anomalies early in life. One of them died from SCT after leukemic transformation. The third patient has developed severe osteoporosis and diabetes mellitus type 1. The fourth is on continuous G-CSF treatment. Our data demonstrate the importance of hematologic follow-up and regular cytogenetic evaluation of the bone marrow in SBDS patients. Patients with rare SBDS gene mutations seem to develop a more severe phenotype, but it requires a larger patient cohort for statistical proof.