Schimke immuno-osseous dysplasia: a clinicopathological correlation.
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.
Clewing
J Marietta
JM
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Antalfy
Barbara C
BC
Lücke
Thomas
T
Najafian
Behzad
B
Marwedel
Katja M
KM
Hori
Akira
A
Powel
Ralph M
RM
Do
A F Safo
AF
Najera
Lydia
L
SantaCruz
Karen
K
Hicks
M John
MJ
Armstrong
Dawna L
DL
Boerkoel
Corndins F
CF
D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000473:pathology; D001344:Autopsy; D001921:Brain / Q000473:pathology; D019902:Chondrocytes / Q000473:pathology; D004265:DNA Helicases / Q000235:genetics*; D017809:Fatal Outcome; D005269:Femur / Q000473:pathology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D009154:Mutation; D009206:Myocardium / Q000473:pathology; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology*; D010902:Pituitary Gland / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D013737:Testis / Q000473:pathology
C412482:SMARCAL1 protein, human; D004265:DNA Helicases