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

doi:10.1016/S0022-3476(99)70332-X

The Journal of Pediatrics

Volume 135, Issue 1, July 1999, Pages 81-88

https://doi.org/10.1016/S0022-3476(99)70332-X Get rights and content

Abstract

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 χ² 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. (J Pediatr 1999;135:81-8.)

Section snippets

Patient Ascertainment

Between 1992 and 1997 we used several strategies to identify patients with SS. We contacted selected pediatric gastroenterologists throughout the world and communicated details of the study at medical and scientific meetings and through newsletters of a parent support group. Some patients were identified by personal contact between families. Clinical data were collected from 116 families with at least 1 member thought to have SS. The patient’s physician and family completed questionnaires

Patients

Among 129 patients from 116 families, 88 patients (75 families: 33 female; median age 5.2 years, range 0.2 to 31.9 years) fulfilled our diagnostic criteria. Most patients (n = 28) were excluded because of incomplete data; 12 did not meet the diagnostic criteria, and in 1 patient a bone marrow biopsy confirmed the diagnosis of Pearson syndrome.²⁵ The median age at diagnosis was 1 year (n = 84; range 0.1 to 13.0 years). Sixty-three patients were isolated cases, whereas 25 were from 12 multiplex

DISCUSSION

Analysis of this large patient cohort provided an opportunity to define the phenotypic spectrum of patients with SS. Consistent with previous reports,1, 2, 3, 4 we found a range of clinical manifestations among affected individuals. Although pancreatic and hematologic abnormalities were used as inclusion criteria, there was considerable variability in the degree of pancreatic dysfunction and the type and severity of hematologic abnormality. We also observed considerable heterogeneity in the

Acknowledgements

We are indebted to all the patients and their families who willingly participated in this study. We gratefully acknowledge the many members of Shwachman-Diamond International, Shwachman-Diamond Canada, Shwachman Support of Great Britain, and the Harrison Wright Appeal for their support and encouragement. We thank the many physicians who provided patient information and blood samples and Lenny Chong for many hours of work devoted to data entry.

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^☆: H.G. was supported by a Duncan Gordon Fellowship, The Hospital for Sick Children Foundation and a research fellowship from the Canadian Association of Gastroenterology. J.M.R. is a scholar of the Medical Research Council of Canada and is a member of the Canadian Genetic Diseases Network. The study was supported by Pediatric Consultants, Inc.

^☆☆: Reprint requests: P.R. Durie, MD, Division of Gastroenterology and Nutrition, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada, M5G 1X8.

^★: 0022-3476/99/$8.00 + 0 9/21/99108

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Shwachman syndrome: Phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar☆,☆☆,★

Abstract

Section snippets

Patient Ascertainment

Patients

DISCUSSION

Acknowledgements

J Pediatr

Gastroenterology

Gastroenterology

J Pediatr

Gastroenterology

Blood

Blood

Shwachman’s syndrome, a review of 21 cases

Arch Dis Child

Frequent myocardial lesions in Shwachman’s syndrome. Eight fatal cases among 16 Finnish patients

Acta Paediatr Scand

Syndrome of Shwachman and leukemia

Scand J Haematol

Haematological abnormalities in Shwachman-Diamond syndrome

Br J Haematol

Association of pancreatic insufficiency and chronic neutropenia in childhood

Arch Dis Child

The syndrome of exocrine pancreatic insufficiency, neutropenia, metaphyseal dysostosis and dwarfism

Helv Paediatr Acta

Metaphyseal chondrodysplasia with dwarfism, pancreatic insufficiency and neutropenia

Pediatr Radiol

Metaphyseal chondrodysplasia, neutropenia, and pancreatic insufficiency presenting with respiratory distress in the neonatal period

Arch Dis Child

Congenital hypoplasia of the exocrine pancreas

Acta Paediatr Scan

Pancreatic insufficiency with bone marrow dysfunction (Shwachman-Diamond-Oski-Khaw’s syndrome). Report of a case

Tohoku J Exp Med

The syndrome of congenital pancreatic insufficiency, chronic respiratory disease and chronic liver damage

Acta Paediatr Scan