ORIGINAL ARTICLE

Schimke immuno-osseous dysplasia: a clinicopathological correlation

J Marietta Clewing¹, Barbara C Antalfy², Thomas Lücke³, Behzad Najafian⁴, Katja M Marwedel⁵, Akira Hori⁵, Ralph M Powel⁴, A F Safo Do⁴, Lydia Najera⁶, Karen SantaCruz⁴, M John Hicks², Dawna L Armstrong², Corndins F Boerkoel¹

¹ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
² Department of Pathology, Baylor College of Medicine, Houston, Texas, USA
³ Department of Pediatrics, Hannover Medical School, Hannover, Germany
⁴ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA
⁵ Department of Pathology, Hannover Medical School, Hannover, Germany
⁶ Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA

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

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.

Abbreviations: ARVCM, arrhythmogenic right ventricular cardiomyopathy; CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy; FSGS, focal segmental glomerulosclerosis; H&E, haematoxylin and eosin; SIOD, Schimke immuno-osseous dysplasia; SMARCAL1, swi/snf-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1; TIA, transient ischaemic attack

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?