Schimke immuno-osseous dysplasia: a clinicopathological correlation

J Med Genet. 2007 Feb;44(2):122-30. doi: 10.1136/jmg.2006.044313. Epub 2006 Jul 13.


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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Atherosclerosis / pathology
  • Autopsy
  • Brain / pathology
  • Chondrocytes / pathology
  • DNA Helicases / genetics*
  • Fatal Outcome
  • Femur / pathology
  • Humans
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / pathology
  • Lung / pathology
  • Male
  • Mutation*
  • Myocardium / pathology
  • Osteochondrodysplasias / genetics*
  • Osteochondrodysplasias / pathology*
  • Pituitary Gland / pathology
  • T-Lymphocytes / immunology
  • Testis / pathology


  • SMARCAL1 protein, human
  • DNA Helicases