Shwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar.

OBJECTIVES: With the use of clinical data from a large international cohort, we evaluated and compared affected siblings and isolated cases.

STUDY DESIGN: Data from 116 families were collected, and patients conforming to our predetermined diagnostic criteria were analyzed. Phenotypic manifestations of affected siblings and singletons were compared with the use of t tests, Wilcoxon scores, and chi2 analysis.

RESULTS: Eighty-eight patients (33 female, 55 male; median age 5.20 years) fulfilled our predetermined diagnostic criteria for Shwachman syndrome; 63 patients were isolated cases, and 25 affected siblings were from 12 multiplex families. Steatorrhea was present in 86% (57 of 66), and 91% (78 of 86) displayed a low serum trypsinogen concentration. Patients older than 4 years more often had pancreatic sufficiency. Neutropenia occurred in 98%, anemia in 42%, and thrombocytopenia in 34%. Myelodysplasia or cytogenetic abnormalities were reported in 7 patients. Short stature with normal nutritional status was a prominent feature.

CONCLUSIONS: Clinical features among patients with Shwachman syndrome varied between patients and with age. Similarities in phenotype between isolated cases and affected sibling sets support the hypothesis that Shwachman syndrome is a single disease entity.