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Schimke immuno-osseous dysplasia is a condition characterized by short stature, kidney disease, and a weakened immune system. In people with this condition, short stature is caused by flattened spinal bones (vertebrae), resulting in a shortened neck and trunk. Adult height is typically between 3 and 5 feet. Kidney (renal) disease often leads to life-threatening renal failure and end-stage renal disease (ESRD). Affected individuals also have a shortage of certain immune system cells called T cells. T cells identify foreign substances and defend the body against infection. A shortage of T cells causes a person to be more susceptible to illness.
Other features frequently seen in people with this condition include an exaggerated curvature of the lower back (lordosis); darkened patches of skin (hyperpigmentation), typically on the chest and back; and a broad nasal bridge with a rounded tip of the nose.
Less common signs and symptoms of Schimke immuno-osseous dysplasia include an accumulation of fatty deposits and scar-like tissue in the lining of the arteries (atherosclerosis), reduced blood flow to the brain (cerebral ischemia), migraine-like headaches, an underactive thyroid gland (hypothyroidism), decreased numbers of white blood cells (lymphopenia), underdeveloped hip bones (hypoplastic pelvis), abnormally small head size (microcephaly), a lack of sperm (azoospermia) in males, and irregular menstruation in females.
In severe cases, many signs of Schimke immuno-osseous dysplasia can be present at birth. People with mild cases of this disorder may not develop signs or symptoms until late childhood.
Schimke immuno-osseous dysplasia is a very rare condition. The prevalence in North America is estimated to be one in 1 million to 3 million people.
Mutations in the SMARCAL1 gene increase the risk of Schimke immuno-osseous dysplasia. The SMARCAL1 gene provides instructions for producing a protein whose specific function is unknown. The SMARCAL1 protein can attach (bind) to chromatin, which is the complex of DNA and protein that packages DNA into chromosomes. Based on the function of similar proteins, SMARCAL1 is thought to influence the activity (expression) of other genes through a process known as chromatin remodeling. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development. When DNA is tightly packed, gene expression is lower than when DNA is loosely packed.
Mutations in the SMARCAL1 gene are thought to lead to disease by affecting protein activity, protein stability, or the protein's ability to bind to chromatin. It is not clear if mutations in the SMARCAL1 gene interfere with chromatin remodeling and the expression of other genes.
The mutations associated with Schimke immuno-osseous dysplasia disrupt the usual functions of the SMARCAL1 protein or prevent the production of any functional protein. People who have mutations that cause a complete lack of functional protein tend to have a more severe form of this disorder than those who have mutations that lead to an active but malfunctioning protein. However, in order for people with SMARCAL1 gene mutations to develop Schimke immuno-osseous dysplasia, other currently unknown genetic or environmental factors must also be present.
Approximately half of all people with Schimke immuno-osseous dysplasia do not have identified mutations in the SMARCAL1 gene. In these cases, the cause of the disease is unknown.
Changes in this gene are associated with Schimke immuno-osseous dysplasia.
Mutations in the SMARCAL1 gene are inherited in an autosomal recessive pattern, which means that an increased risk of Schimke immuno-osseous dysplasia results from mutations in both copies of the SMARCAL1 gene in each cell. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
These resources address the diagnosis or management of Schimke immuno-osseous dysplasia and may include treatment providers.
You might also find information on the diagnosis or management of Schimke immuno-osseous dysplasia in Educational resources (http://www.ghr.nlm.nih.gov/condition/schimke-immuno-osseous-dysplasia/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/schimke-immuno-osseous-dysplasia/show/Patient+support).
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
You may find the following resources about Schimke immuno-osseous dysplasia helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
arteries ; atherosclerosis ; autosomal ; autosomal recessive ; azoospermia ; cell ; chromatin ; chromatin remodeling ; DNA ; dysplasia ; end-stage renal disease ; ESRD ; gene ; gene expression ; hypothyroidism ; immune system ; infection ; ischemia ; kidney ; lordosis ; lymphopenia ; menstruation ; microcephaly ; migraine ; pelvis ; prevalence ; protein ; recessive ; renal ; renal disease ; short stature ; sperm ; stage ; stature ; thyroid ; tissue ; white blood cells
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.