Familial Idiopathic Basal Ganglia Calcification

Familial Idiopathic Basal Ganglia Calcification

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Familial Idiopathic Basal Ganglia Calcification is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Fahr disease, formerly
  • FIBGC
  • striopallidodentate calcinosis
  • cerebrovascular ferrocalcinosis

Disorder Subdivisions

  • None

General Discussion

Familial idiopathic basal ganglia calcification (FIBGC) is a rare neurological disorder characterized by the presence of abnormal calcium deposits (calcifications) of unknown cause. Associated symptoms include progressive deterioration of cognitive abilities (dementia), loss of contact with reality (psychosis), mood swings and loss of acquired motor skills. As the condition progresses, paralysis may develop that is associated with increased muscle stiffness (rigidity) and restricted movements (spastic paralysis). Additional abnormalities may include relatively slow, involuntary, continual writhing movements (athetosis) or chorea, a related condition characterized by irregular, rapid, jerky movements.

Symptoms

Familial idiopathic basal ganglia calcification is characterized by abnormal calcium deposits in the basal ganglia, dentate nucleus, thalami and cerebral white matter of the brain and may be found as early as the first decade of life. Neuropsychiatric symptoms usually begin in the third to fifth decade. Early symptoms may include clumsiness, fatigue, slow or slurred speech and difficulty swallowing (dysphagia). Some individuals with basal ganglia calcification remain free of symptoms for several decades. Progressive deterioration of mental abilities (dementia) and loss of previous motor development are accompanied by spastic paralysis and in some cases, twisting movements of the hands and feet (athetosis). Features of Parkinson disease found in this disorder may include tremors and rigidity, a masklike facial expression, shuffling walk, and a pill rolling motion of the fingers. Muscle cramping (dystonia), uncontrollable spasmodic irregular movements (chorea), and seizures can also occur. Occasional symptoms include sensory changes, headaches and urinary incontinence.

Causes

Familial idiopathic basal ganglia calcification is inherited as an autosomal dominant genetic condition. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. It is not known how many cases of FIBGC are due to a new gene mutation. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.



Wang et al (2012) reported 7 families from China, Spain and Brazil, with different mutations in the SLC20A2 gene on chromosome 8, encoding for a phosphate inorganic transporter (PIT-2). Twin studies suggest that there are inherited patterns of basal ganglia calcification that may be linked to specific genes. Other genes on chromosomes 7, 9 and 14 are also being studied to determine if they are associated with FIBGC.

Affected Populations

The prevalence of FIBGC is unknown. Approximately 30 families have been described with this syndrome.

Standard Therapies

Diagnosis

Neuroimaging techniques such as computed tomography (CT) of the brain (the most sensitive technique), magnetic resonance imaging (MRI) and skull X-rays are used to diagnose calcification of the basal ganglia. This finding in combination with a progressive movement disorder, neuropsychiatric problems beginning in the 40's or 50's, a lack of biochemical abnormalities or other known causes (infection, toxic exposure, trauma) make the diagnosis very likely.



Treatment

No specific treatment is known for FIBGC. Medications can be used to treat symptoms associated with this condition, such as movement disorders, seizures, anxiety, depression, psychosis and urinary incontinence.



Genetic counseling is recommended for affected individuals and their families, especially for those with mutations at the SLC20A2 gene.

Investigational Therapies

Speech and gait were improved in one patient treated with disodium etidronate, but other neurologic symptoms and calcification were unchanged.



Levodopa therapy was found to be effective in treating parkinsonian features in one individual who had FIBGC and Parkinson disease.



The anticonvulsant oxcarbazepine was effective in treating a Turkish patient with basal ganglia calcification and dyskinesia.



Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:



www.centerwatch.com



Contact for additional information about familial idiopathic basal ganglia calcification:



João Ricardo Mendes de Oliveira, MD, PhD

Federal University of Pernambuco

Av. Prof. Moraes Rego, 1235

Cidade Universitária, Recife

PE, 50670-901, Brazil

Phone: 55-81-87819856

joao.ricardo@ufpe.br

References

TEXTBOOKS

Oliveira JRM. Managing Idiopathic Basal Ganglia Calcification ("Fahr's Disease"). New York: Nova Publishing; 2011.



Manyam BV. Fahr Disease. In: The NORD Guide to Rare Disorders. Lippincott, Williams and Wilkins; 2003:532.



JOURNAL ARTICLES

Wang C, Li Y, Shi L, et al. Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet. 2012;44(3):254-256.



Oliveira JR, Lima Filho JL, Zatz M. Identical twins with idiopathic basal ganglia calcification ("Fahr's disease") presenting with a remarkably similar pattern of neuroimaging findings. Parkinsonism Relat Disord. 2009:15:396-397.



Alemdar M, Selek A, Iseri P, et al. Fahr's disease presenting with paroxysmal non-kinesigenic dyskinesia: a case report. Parkinsonism Relat Disord. 2008;14(1):69-71.

Weisman DC, Yaari R, Hansen LA, Thal LJ. Density of the brain, decline of the mind: an atypical case of Fahr disease. Arch Neurol. 2007; 64:756-7.



Baba Y, Broderick DF, Uitti RJ, et al. Heredofamilial brain calcinosis syndrome. Mayo Clin Proc. 2005;80(5):641-51.



Manyam BV. What is and what is not 'Fahr's disease'. Parkinsonism Relat Disord. 2005; 11:73-80.



Modrego PJ, Mojonero J, Serrano M, Fayed N. Fahr's syndrome presenting with pure and progressive presenile dementia. Neurol Sci. 2005; 26:367-9.



Oliveira JR, Spiteri E, Sobrido MJ, et al. Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr disease). Neurology. 2004;63:2165-7.



Oliveira JR, Hopfer S, Papp J, et al. A genome-wide scan for familial idiopathic basal ganglia calcification (Fahr's disease) identifies new candidate regions and confirms genetic heterogeneity. Am J Hum Genet 2003; 73(5):570.



Manyam BV, Walters AS, Keller IA, Ghobrial M. Parkinsonism associated with autosomal dominant bilateral striopallidodentate calcinosis. Parkinsonism Relat Disord. 2001;7:289.



Manyam BV, Walters AS, Narla KR. Bilateral striopallidodentate calcinosis: clinical characteristics of patients seen in a registry. Mov Disord. 2001;16:258-64.



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;65:764-72.



INTERNET

Sobrido MJ, Hopfer S, Geschwind DH. (Updated September 20, 2007). Familial Idiopathic Basal Ganglia Calcification. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1993-2012. Available at http://www.genetests.org. Accessed February 28, 2012.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Basal Ganglia Calcification, Idiopathic,1; IBGC1. Entry No: 213600. Last Edited September 11, 2009. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed February 28, 2012.

Resources

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For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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