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J Med Genet 44:122-130 doi:10.1136/jmg.2006.044313
  • Original article

Schimke immuno-osseous dysplasia: a clinicopathological correlation

  1. J Marietta Clewing1,
  2. Barbara C Antalfy2,
  3. Thomas Lücke3,
  4. Behzad Najafian4,
  5. Katja M Marwedel5,
  6. Akira Hori5,
  7. Ralph M Powel4,
  8. A F Safo Do4,
  9. Lydia Najera6,
  10. Karen SantaCruz4,
  11. M John Hicks2,
  12. Dawna L Armstrong2,
  13. Corndins F Boerkoel1
  1. 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
  2. 2Department of Pathology, Baylor College of Medicine, Houston, Texas, USA
  3. 3Department of Pediatrics, Hannover Medical School, Hannover, Germany
  4. 4Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA
  5. 5Department of Pathology, Hannover Medical School, Hannover, Germany
  6. 6Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
  1. Correspondence to:
 Dr C F Boerkoel
 Department of Medical Genetics, Children’s and Women’s Health Centre of British Columbia, University of British Columbia, 4500 Oak Street, Rm C234, Vancouver, Canada, BC V6H 3N1; boerkoel{at}interchange.ubc.ca
  • Received 25 May 2006
  • Accepted 27 June 2006
  • Revised 24 June 2006
  • Published Online First 13 July 2006

Abstract

Background: Schimke immuno-osseous dysplasia (SIOD) is a fatal autosomal recessive disorder caused by loss-of-function mutations in swi/snf-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1).

Methods: Analysis of detailed autopsies to correlate clinical and pathological findings in two men severely affected with SIOD.

Results: As predicted by the clinical course, T cell deficiency in peripheral lymphoid organs, defective chondrogenesis, focal segmental glomerulosclerosis, cerebral ischaemic lesions and premature atherosclerosis were identified. Clinically unexpected findings included a paucity of B cells in the peripheral lymphoid organs, emperipolesis-like (penetration of one cell by another) abnormalities in the adenohypophysis, fatty infiltration of the cardiac right ventricular wall, pulmonary emphysema, testicular hypoplasia with atrophy and azospermia, and clustering of small cerebral vessels.

Conclusions: A regulatory role for the SMARCAL1 protein in the proliferation of chondrocytes, lymphocytes and spermatozoa, as well as in the development or maintenance of cardiomyocytes and in vascular homoeostasis, is suggested. Additional clinical management guidelines are recommended as this study has shown that patients with SIOD may be at risk of pulmonary hypertension, combined immunodeficiency, subcortical ischaemic dementia and cardiac dysfunction.

Footnotes

  • Published Online First 13 July 2006