The main clinical features are spondyloepiphyseal dysplasia and short stature, defective cellular immunity with increased susceptibility to life-threatening infections and a progressive steroid-resistant nephrotic syndrome that leads to end-stage renal failure in nearly two thirds of patients. Hypertension and proteinuria are early common features of SIOD. Almost all patients have T-cell deficiency with a normal CD4/CD8 ratio. Hyperpigmented macules, thin hair and dysmorphic facial features (a triangular-shaped face, broad depressed nasal bridge, narrow nasal ridge and a broad nasal tip) are common. Neurologic manifestations include atherosclerosis and cerebrovascular disease, which manifest as migraine-like headaches, cerebral ischemia, cardiac dysfunction and cognitive deficiency. Additional features may include hypothyroidism, enteropathy, and normocytic or microcytic anemia. The teeth have a yellowish grey discoloration, bulbous crowns and marked cervical constriction of the primary and permanent molars. The pulp chambers are small or obliterated. Both enamel and dentin are softer than normal.
Schimke immuno-osseous dysplasia is caused by mutations in the SMARCAL1 gene (2q35) which encodes the chromatin remodeling protein hHARP (also known as the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1).
