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Genetics Home Reference: your guide to understanding genetic conditions
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Familial idiopathic basal ganglia calcification

(often shortened to FIBGC)
Reviewed February 2013

What is FIBGC?

Familial idiopathic basal ganglia calcification (FIBGC, formerly known as Fahr disease) is a condition characterized by abnormal deposits of calcium (calcification) in the brain. These calcium deposits typically occur in the basal ganglia, which are structures deep within the brain that help start and control movement; however, other brain regions can also be affected.

The signs and symptoms of FIBGC include movement disorders and psychiatric or behavioral difficulties. These problems begin in adulthood, usually in a person's thirties. The movement difficulties experienced by people with FIBGC include involuntary tensing of various muscles (dystonia), problems coordinating movements (ataxia), and uncontrollable movements of the limbs (choreoathetosis). Affected individuals often have seizures as well. The psychiatric and behavioral problems include difficulty concentrating, memory loss, changes in personality, a distorted view of reality (psychosis), and decline in intellectual function (dementia). An estimated 20 to 30 percent of people with FIBGC have one of these psychiatric disorders.

The severity of this condition varies among affected individuals; some people have no symptoms related to the brain calcification, whereas other people have significant movement and psychiatric problems.

How common is FIBGC?

FIBGC is thought to be a rare disorder; about 60 affected families have been described in the medical literature. However, because brain imaging tests are needed to recognize the calcium deposits, this condition is believed to be underdiagnosed.

What genes are related to FIBGC?

Mutations in the SLC20A2 gene cause nearly half of all cases of FIBGC. A small percentage of cases are caused by mutations in the PDGFRB gene. Other cases of FIBGC appear to be associated with changes in chromosomes 2, 7, 9, and 14, although specific genes have yet to be identified. These findings suggest that multiple genes are involved in this condition.

The SLC20A2 gene provides instructions for making a protein called sodium-dependent phosphate transporter 2 (PiT-2). This protein plays a major role in regulating phosphate levels within the body (phosphate homeostasis) by transporting phosphate across cell membranes. The SLC20A2 gene mutations that cause FIBGC lead to the production of a PiT-2 protein that cannot effectively transport phosphate into cells. As a result, phosphate levels in the bloodstream rise. In the brain, the excess phosphate combines with calcium and forms deposits.

The PDGFRB gene provides instructions for making a protein that plays a role in turning on (activating) signaling pathways that control many cell processes. It is unclear how PDGFRB gene mutations cause FIBGC. Mutations may alter signaling within cells that line blood vessels in the brain, causing them to take in excess calcium, and leading to calcification of the lining of these blood vessels. Alternatively, changes in the PDGFRB protein could alter phosphate transport signaling pathways, causing an increase in phosphate levels and the formation of calcium deposits.

Researchers suggest that calcium deposits lead to the characteristic features of FIBGC by interrupting signaling pathways in various parts of the brain. Calcium deposits may disrupt the pathways that connect the basal ganglia to other areas of the brain, particularly the frontal lobes. These areas at the front of the brain are involved in reasoning, planning, judgment, and problem-solving. The regions of the brain that regulate social behavior, mood, and motivation may also be affected.

Research has shown that people with significant calcification tend to have more signs and symptoms of FIBGC than people with little or no calcification. However, this association does not apply to all people with FIBGC.

Related Gene(s)

Changes in these genes are associated with familial idiopathic basal ganglia calcification.

  • PDGFRB
  • SLC20A2

How do people inherit FIBGC?

FIBGC is inherited in an autosomal dominant pattern. Autosomal dominant inheritance means one copy of an altered SLC20A2 or PDGFRB gene in each cell is sufficient to cause the disorder. This condition appears to follow an autosomal dominant pattern of inheritance when the genetic cause is not known. In most cases, an affected person has one parent with the condition.

Where can I find information about diagnosis or management of FIBGC?

These resources address the diagnosis or management of FIBGC and may include treatment providers.

  • Dystonia Medical Research Foundation: Treatments (http://dystonia-foundation.org/living-with-dystonia/treatments)
  • Gene Review: Primary Familial Brain Calcification (http://www.ncbi.nlm.nih.gov/books/NBK1421)
  • Genetic Testing Registry: Basal ganglia calcification, idiopathic, 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1847731)
  • Genetic Testing Registry: Idiopathic basal ganglia calcification 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0393590)

You might also find information on the diagnosis or management of FIBGC in Educational resources (http://www.ghr.nlm.nih.gov/condition/familial-idiopathic-basal-ganglia-calcification/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/familial-idiopathic-basal-ganglia-calcification/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 FIBGC?

You may find the following resources about FIBGC 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.

What other names do people use for FIBGC?

  • bilateral striopallidodentate calcinosis
  • cerebrovascular ferrocalcinosis
  • striopallidodentate calcinosis

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.

What if I still have specific questions about FIBGC?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding FIBGC?

ataxia ; autosomal ; autosomal dominant ; bilateral ; calcification ; calcinosis ; calcium ; cell ; dementia ; dystonia ; familial ; gene ; homeostasis ; idiopathic ; imaging ; inheritance ; inherited ; involuntary ; pattern of inheritance ; phosphate ; protein ; psychosis ; sodium ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Dai X, Gao Y, Xu Z, Cui X, Liu J, Li Y, Xu H, Liu M, Wang QK, Liu JY. Identification of a novel genetic locus on chromosome 8p21.1-q11.23 for idiopathic basal ganglia calcification. Am J Med Genet B Neuropsychiatr Genet. 2010 Oct 5;153B(7):1305-10. doi: 10.1002/ajmg.b.31102. (http://www.ncbi.nlm.nih.gov/pubmed/20552677?dopt=Abstract)
  • Geschwind DH, Loginov M, Stern JM. Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease). Am J Hum Genet. 1999 Sep;65(3):764-72. (http://www.ncbi.nlm.nih.gov/pubmed/10441584?dopt=Abstract)
  • Hsu SC, Sears RL, Lemos RR, Quintáns B, Huang A, Spiteri E, Nevarez L, Mamah C, Zatz M, Pierce KD, Fullerton JM, Adair JC, Berner JE, Bower M, Brodaty H, Carmona O, Dobricić V, Fogel BL, García-Estevez D, Goldman J, Goudreau JL, Hopfer S, Janković M, Jaumà S, Jen JC, Kirdlarp S, Klepper J, Kostić V, Lang AE, Linglart A, Maisenbacher MK, Manyam BV, Mazzoni P, Miedzybrodzka Z, Mitarnun W, Mitchell PB, Mueller J, Novaković I, Paucar M, Paulson H, Simpson SA, Svenningsson P, Tuite P, Vitek J, Wetchaphanphesat S, Williams C, Yang M, Schofield PR, de Oliveira JR, Sobrido MJ, Geschwind DH, Coppola G. Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification. Neurogenetics. 2013 Feb;14(1):11-22. doi: 10.1007/s10048-012-0349-2. Epub 2013 Jan 20. (http://www.ncbi.nlm.nih.gov/pubmed/23334463?dopt=Abstract)
  • Manyam BV. What is and what is not 'Fahr's disease'. Parkinsonism Relat Disord. 2005 Mar;11(2):73-80. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15734663?dopt=Abstract)
  • Nicolas G, Pottier C, Maltête D, Coutant S, Rovelet-Lecrux A, Legallic S, Rousseau S, Vaschalde Y, Guyant-Maréchal L, Augustin J, Martinaud O, Defebvre L, Krystkowiak P, Pariente J, Clanet M, Labauge P, Ayrignac X, Lefaucheur R, Le Ber I, Frébourg T, Hannequin D, Campion D. Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification. Neurology. 2013 Jan 8;80(2):181-7. doi: 10.1212/WNL.0b013e31827ccf34. Epub 2012 Dec 19. (http://www.ncbi.nlm.nih.gov/pubmed/23255827?dopt=Abstract)
  • Oliveira JR, Sobrido MJ, Spiteri E, Hopfer S, Meroni G, Petek E, Baquero M, Geschwind DH. Analysis of candidate genes at the IBGC1 locus associated with idiopathic basal ganglia calcification ("Fahr's disease"). J Mol Neurosci. 2007;33(2):151-4. (http://www.ncbi.nlm.nih.gov/pubmed/17917073?dopt=Abstract)
  • Oliveira JR, Spiteri E, Sobrido MJ, Hopfer S, Klepper J, Voit T, Gilbert J, Wszolek ZK, Calne DB, Stoessl AJ, Hutton M, Manyam BV, Boller F, Baquero M, Geschwind DH. Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr disease). Neurology. 2004 Dec 14;63(11):2165-7. (http://www.ncbi.nlm.nih.gov/pubmed/15596772?dopt=Abstract)
  • Saiki M, Saiki S, Sakai K, Matsunari I, Higashi K, Murata KY, Hattori N, Hirose G. Neurological deficits are associated with increased brain calcinosis, hypoperfusion, and hypometabolism in idiopathic basal ganglia calcification. Mov Disord. 2007 May 15;22(7):1027-30. (http://www.ncbi.nlm.nih.gov/pubmed/17357130?dopt=Abstract)
  • Shirahama M, Akiyoshi J, Ishitobi Y, Tanaka Y, Tsuru J, Matsushita H, Hanada H, Kodama K. A young woman with visual hallucinations, delusions of persecution and a history of performing arson with possible three-generation Fahr disease. Acta Psychiatr Scand. 2010 Jan;121(1):75-7. doi: 10.1111/j.1600-0447.2009.01423.x. Epub 2009 Jun 12. (http://www.ncbi.nlm.nih.gov/pubmed/19522881?dopt=Abstract)
  • Volpato CB, De Grandi A, Buffone E, Facheris M, Gebert U, Schifferle G, Schönhuber R, Hicks A, Pramstaller PP. 2q37 as a susceptibility locus for idiopathic basal ganglia calcification (IBGC) in a large South Tyrolean family. J Mol Neurosci. 2009 Nov;39(3):346-53. doi: 10.1007/s12031-009-9287-3. (http://www.ncbi.nlm.nih.gov/pubmed/19757205?dopt=Abstract)
  • Wang C, Li Y, Shi L, Ren J, Patti M, Wang T, de Oliveira JR, Sobrido MJ, Quintáns B, Baquero M, Cui X, Zhang XY, Wang L, Xu H, Wang J, Yao J, Dai X, Liu J, Zhang L, Ma H, Gao Y, Ma X, Feng S, Liu M, Wang QK, Forster IC, Zhang X, Liu JY. Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet. 2012 Feb 12;44(3):254-6. doi: 10.1038/ng.1077. (http://www.ncbi.nlm.nih.gov/pubmed/22327515?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 healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2013
Published: December 16, 2014