Reviewed November 2008
What is Schimke immuno-osseous dysplasia?
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.
How common is Schimke immuno-osseous dysplasia?
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.
What genes are related to Schimke immuno-osseous dysplasia?
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.
How do people inherit 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.
Where can I find information about diagnosis or management of Schimke immuno-osseous dysplasia?
These resources address the diagnosis or management of Schimke immuno-osseous dysplasia and may include treatment providers.
- Gene Review: Schimke Immunoosseous Dysplasia (http://www.ncbi.nlm.nih.gov/books/NBK1376)
- Genetic Testing Registry: Schimke immunoosseous dysplasia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0877024)
You might also find information on the diagnosis or management of Schimke immuno-osseous dysplasia in
Educational resources (http://ghr.nlm.nih.gov/condition/schimke-immuno-osseous-dysplasia/show/Educational+resources) and Patient support (http://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.
Where can I find additional information about Schimke immuno-osseous dysplasia?
You may find the following resources about Schimke immuno-osseous dysplasia helpful. These materials are written for the general public.
MedlinePlus - Health information
- Health Topic: Bone Diseases (http://www.nlm.nih.gov/medlineplus/bonediseases.html)
- Health Topic: Dwarfism (http://www.nlm.nih.gov/medlineplus/dwarfism.html)
- Health Topic: Immune System and Disorders (http://www.nlm.nih.gov/medlineplus/immunesystemanddisorders.html)
- Health Topic: Kidney Failure (http://www.nlm.nih.gov/medlineplus/kidneyfailure.html)
- Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/4984/schimke-immunoosseous-dysplasia/resources/1)
Additional NIH Resources - National Institutes of Health
- National Institute of Allergy and Infectious Diseases: Disorders of the Immune System (http://www.niaid.nih.gov/topics/immuneSystem/Pages/immuneDisorders.aspx)
- National Institute of Diabetes and Digestive and Kidney Diseases: Hyperthyroidism (http://www.endocrine.niddk.nih.gov/pubs/Hyperthyroidism/)
Educational resources - Information pages
- Boston Children's Hospital: Kidney Failure (http://www.childrenshospital.org/health-topics/conditions/kidney-failure)
- Boston Children's Hospital: Primary Immunodeficiency (http://www.childrenshospital.org/health-topics/conditions/p/primary-immunodeficiency)
- Cedars-Sinai Medical Center: International Skeletal Dysplasia Registry (http://isdr.csmc.edu/)
- MalaCards: schimke immunoosseous dysplasia (http://www.malacards.org/card/schimke_immunoosseous_dysplasia)
- Merck Manual Home Edition for Patients and Caregivers: CChronic Kidney Disease (http://www.merckmanuals.com/home/kidney_and_urinary_tract_disorders/kidney_failure/chronic_kidney_disease.html?qt=&sc=&alt=)
- National Health Service (UK) Clinical Knowledge Summaries: Chronic Kidney Disease (http://www.nhs.uk/conditions/kidney-disease-chronic/pages/introduction.aspx)
- Nemours Children's Health System: Skeletal Dysplasia (http://www.nemours.org/service/medical/skeletal-dysplasia.html?tab=about)
- Orphanet: Schimke immuno-osseous dysplasia (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=1830)
Patient support - For patients and families
- Human Growth Foundation (http://www.hgfound.org/)
- Little People of America (http://www.lpaonline.org/)
- National Kidney Foundation (https://www.kidney.org/)
- National Organization for Rare Disorders (NORD) (https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1198/viewAbstract)
- The MAGIC Foundation (http://www.magicfoundation.org/www)
- University of Kansas Medical Center: Dwarfism/Short Stature (http://www.kumc.edu/gec/support/skeldysp.html)
- University of Kansas Medical Center Resource List: Immune Deficiency Conditions (http://www.kumc.edu/gec/support/immune.html)
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1376)
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Schimke immunoosseous dysplasia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0877024)
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28schimke%20immunoosseous%20dysplasia%5BTIAB%5D%29%20OR%20%28schimke%20immuno-osseous%20dysplasia%5BTIAB%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/242900)
What other names do people use for Schimke immuno-osseous dysplasia?
- immunoosseous dysplasia, Schimke type
- Schimke immunoosseous dysplasia
For more information about naming genetic conditions, see the Genetics Home Reference
Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide)
How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What if I still have specific questions about Schimke immuno-osseous dysplasia?
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).
What glossary definitions help with understanding Schimke immuno-osseous dysplasia?
autosomal recessive ;
chromatin remodeling ;
end-stage renal disease ;
gene expression ;
immune system ;
renal disease ;
short stature ;
white blood cells
You may find definitions for these and many other terms in the Genetics Home Reference
- Boerkoel CF, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L, André JL, Bogdanovic R, Burguet A, Cockfield S, Cordeiro I, Fründ S, Illies F, Joseph M, Kaitila I, Lama G, Loirat C, McLeod DR, Milford DV, Petty EM, Rodrigo F, Saraiva JM, Schmidt B, Smith GC, Spranger J, Stein A, Thiele H, Tizard J, Weksberg R, Lupski JR, Stockton DW. Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia. Nat Genet. 2002 Feb;30(2):215-20. Epub 2002 Jan 22. (http://www.ncbi.nlm.nih.gov/pubmed/11799392?dopt=Abstract)
- Clewing JM, Fryssira H, Goodman D, Smithson SF, Sloan EA, Lou S, Huang Y, Choi K, Lücke T, Alpay H, André JL, Asakura Y, Biebuyck-Gouge N, Bogdanovic R, Bonneau D, Cancrini C, Cochat P, Cockfield S, Collard L, Cordeiro I, Cormier-Daire V, Cransberg K, Cutka K, Deschenes G, Ehrich JH, Fründ S, Georgaki H, Guillen-Navarro E, Hinkelmann B, Kanariou M, Kasap B, Kilic SS, Lama G, Lamfers P, Loirat C, Majore S, Milford D, Morin D, Ozdemir N, Pontz BF, Proesmans W, Psoni S, Reichenbach H, Reif S, Rusu C, Saraiva JM, Sakallioglu O, Schmidt B, Shoemaker L, Sigaudy S, Smith G, Sotsiou F, Stajic N, Stein A, Stray-Pedersen A, Taha D, Taque S, Tizard J, Tsimaratos M, Wong NA, Boerkoel CF. Schimke immunoosseous dysplasia: suggestions of genetic diversity. Hum Mutat. 2007 Mar;28(3):273-83. (http://www.ncbi.nlm.nih.gov/pubmed/17089404?dopt=Abstract)
- Deguchi K, Clewing JM, Elizondo LI, Hirano R, Huang C, Choi K, Sloan EA, Lücke T, Marwedel KM, Powell RD Jr, Santa Cruz K, Willaime-Morawek S, Inoue K, Lou S, Northrop JL, Kanemura Y, van der Kooy D, Okano H, Armstrong DL, Boerkoel CF. Neurologic phenotype of Schimke immuno-osseous dysplasia and neurodevelopmental expression of SMARCAL1. J Neuropathol Exp Neurol. 2008 Jun;67(6):565-77. doi: 10.1097/NEN.0b013e3181772777. (http://www.ncbi.nlm.nih.gov/pubmed/18520775?dopt=Abstract)
- Elizondo LI, Cho KS, Zhang W, Yan J, Huang C, Huang Y, Choi K, Sloan EA, Deguchi K, Lou S, Baradaran-Heravi A, Takashima H, Lücke T, Quiocho FA, Boerkoel CF. Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation. J Med Genet. 2009 Jan;46(1):49-59. doi: 10.1136/jmg.2008.060095. Epub 2008 Sep 19. (http://www.ncbi.nlm.nih.gov/pubmed/18805831?dopt=Abstract)
- Lou S, Lamfers P, McGuire N, Boerkoel CF. Longevity in Schimke immuno-osseous dysplasia. J Med Genet. 2002 Dec;39(12):922-5. (http://www.ncbi.nlm.nih.gov/pubmed/12471207?dopt=Abstract)
- Lücke T, Clewing JM, Boerkoel CF, Hartmann H, Das AM, Knauth M, Becker H, Donnerstag F. Cerebellar atrophy in Schimke-immuno-osseous dysplasia. Am J Med Genet A. 2007 Sep 1;143A(17):2040-5. (http://www.ncbi.nlm.nih.gov/pubmed/17676601?dopt=Abstract)
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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.