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Schimke immuno-osseous dysplasia

Orpha number ORPHA1830
Synonym(s) Schimke syndrome
Spondyloepiphyseal dysplasia - nephrotic syndrome
Prevalence <1 / 1 000 000
Inheritance
  • Autosomal recessive
Age of onset Neonatal/infancy
ICD-10 -
OMIM
UMLS
  • C0877024
MeSH
  • C536629
MedDRA
  • 10048699
SNOMED CT -

Summary

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.

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.

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.

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).

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.

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

SIOD is an autosomal recessive disorder.

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.

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.

Expert reviewer(s)

  • Pr Raoul HENNEKAM

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Detailed information

Clinical genetics review
  • EN (2013)
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