Schimke Immuno-Osseous Dysplasia

Schimke immuno-osseous dysplasia (SIOD) is a multisystem disorder characterized by spondyloepiphyseal dysplasia and disproportionate short stature, facial dysmorphism, T-cell immunodeficiency, and glomerulonephritis with nephrotic syndrome.

Epidemiology

Approximately 50 cases have been reported in the literature so far, without any apparent sex, ethnic or geographic predilection. In North America, the prevalence of SIOD is estimated at 1 in 1-3 million live births.

Clinical description

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.

Etiology

SIOD 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).

Diagnostic methods

Diagnosis is based on careful clinical, biochemical and radiologic evaluation with osteopenia, ovoid and flattened vertebral bodies, and hypoplastic femoral heads and acetabular roofs being the typical radiographic characteristics. Molecular testing may be performed to confirm the diagnosis.

Differential diagnosis

Cartilage-hair hypoplasia (see this term) is the main differential diagnosis.

Genetic counseling

SIOD is an autosomal recessive disorder.

Management and treatment

As the disease affects multiple body systems, management requires a multi-specialist therapeutic approach. Kidney transplantation is the therapy of choice for end-stage renal failure. Due to the underlying immune disorder in SIOD, however, immunosuppressive therapy after renal transplantation remains associated with increased risk of rejection and severe opportunistic infections.

Prognosis

Life expectancy is limited to childhood or early adolescence in most patients, due to stroke, infections, bone marrow failure, and renal failure. Survival into adulthood has been reported for patients with milder late-onset forms of the disease and successful management of the renal manifestations.