Schimke immuno-osseous dysplasia (OMIM 242900) is an uncommon 
autosomal-recessive multisystem disease caused by mutations in SMARCAL1 
(swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, 
subfamily a-like 1), a gene encoding a putative chromatin remodeling protein. 
Neurologic manifestations identified to date relate to enhanced atherosclerosis 
and cerebrovascular disease. Based on a clinical survey, we determined that half 
of Schimke immuno-osseous dysplasia patients have a small head circumference, 
and 15% have social, language, motor, or cognitive abnormalities. Postmortem 
examination of 2 Schimke immuno-osseous dysplasia patients showed low brain 
weights and subtle brain histologic abnormalities suggestive of perturbed 
neuron-glial migration such as heterotopia, irregular cortical thickness, 
incomplete gyral formation, and poor definition of cortical layers. We found 
that SMARCAL1 is highly expressed in the developing and adult mouse and human 
brain, including neural precursors and neuronal lineage cells. These 
observations suggest that SMARCAL1 deficiency may influence brain development 
and function in addition to its previously recognized effect on cerebral 
circulation.