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Disease Profile

Primary Familial Brain Calcification

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Adult

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ICD-10

G23.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

FIBGC (formerly); Idiopathic basal ganglia calcification 1; Fahr's Syndrome (formerly);

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Primary familial brain calcification (PFBC) is a neurodegenerative disorder characterized by calcium deposits in the basal ganglia, a part of the brain that helps start and control movement. The first symptoms often include clumsiness, fatigue, unsteady walking (gait), slow or slurred speech, difficulty swallowing (dysphagia) and dementia. Migraines and seizures frequently occur. Symptoms typically start in an individual's 30's to 40's but may begin at any age.The neuropsychiatric symptoms and movement disorders worsen over time. Mutations in the SLC20A2PDGFRB, and PDGFB genes have been found to cause PFBC. This condition is inherited in an autosomal dominant manner.[1][2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of neuronal migration
0002269
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Hepatomegaly
Enlarged liver
0002240
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Seizure
0001250
Subcutaneous hemorrhage
Bleeding below the skin
0001933
Thrombocytopenia
Low platelet count
0001873
Ventriculomegaly
0002119
30%-79% of people have these symptoms
Corneal opacity
0007957
5%-29% of people have these symptoms
Abnormal pyramidal sign
0007256
Percent of people who have these symptoms is not available through HPO
Adult onset
Symptoms begin in adulthood
0003581
Athetosis
Involuntary writhing movements in fingers, hands, toes, and feet
0002305
Autosomal dominant inheritance
0000006
Basal ganglia calcification
0002135
Bradykinesia
Slow movements
Slowness of movements

[ more ]

0002067
Calcification of the small brain vessels
0002504
Chorea
0002072
Dense calcifications in the cerebellar dentate nucleus
0002461
Depressivity
Depression
0000716
Dysarthria
Difficulty articulating speech
0001260
Dysdiadochokinesis
Difficulty performing quick and alternating movements
0002075
Dystonia
0001332
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Hyperreflexia
Increased reflexes
0001347
Limb dysmetria
0002406
Mask-like facies
Expressionless face
Lack of facial expression
Mask-like facial appearance

[ more ]

0000298
Memory impairment
Forgetfulness
Memory loss
Memory problems
Poor memory

[ more ]

0002354
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline

[ more ]

0001268
Micrographia
0031908
Parkinsonism
0001300
Postural instability
Balance impairment
0002172
Progressive
Worsens with time
0003676
Psychosis
0000709
Rigidity
Muscle rigidity
0002063
Tremor
0001337
Urinary incontinence
Loss of bladder control
0000020

Cause

PFBC is a genetic condition. Mutations in the SLC20A2 gene are thought to cause about half of the cases of PFBC. Mutations in the PDGFRB and PDGFB genes have also been shown to cause PFBC. In some cases, the genes responsible have not yet been found.[1][2]

Diagnosis

The diagnosis of PFBC relies upon:[1]

1) visualization of bilateral (on both sides) calcification of the basal ganglia on neuroimaging, 
2) presence of progressive neurological dysfunction, 
3) absence of a metabolic, infectious, toxic, or traumatic cause, and
4) a family history consistent with autosomal dominant inheritance (a person must inherit one copy of the altered gene from one parent to have the condition).

Molecular genetic testing can help confirm the diagnosis.[1]

Genetic testing may help to confirm the diagnosis. For individuals in who a diagnosis of PFBC is being considered, other causes of brain calcification should be eliminated prior to pursuing genetic testing, particularly in simplex cases. Testing that might be done includes biochemical analysis of blood and urine, as well as analysis of cerebrospinal fluid. If no other primary cause for brain calcification is detected or if the family history is suggestive of autosomal dominant inheritance, molecular genetic testing should be considered.[1] 

Sequencing of SLC20A2 should be pursued first. If no mutation is identified, deletion/duplication analysis of SLC20A2 may be considered. If no identifiable mutation or deletion in SLC20A2 is found, sequence analysis of PDGFRB and PDGFB may be considered.[1]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    There is no standard course of treatment for PFBC. Treatment typically addresses symptoms on an individual basis. Medications may be used to improve anxiety, depression, obsessive-compulsive behaviors, and dystoniaAntiepileptic drugs (AEDs) can be prescribed for seizures. Oxybutynin may be prescribed for urinary incontinence (loss of bladder control). Surveillance typically includes yearly neurologic and neuropsychiatric assessments.[1]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Primary Familial Brain Calcification. Click on the link to view a sample search on this topic.

            References

            1. Sobrido MJ, Coppola G, Oliveira J, Hopfer S, Geschwind DH. Primary Familial Brain Calcification. GeneReviews. October 16, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1421/.
            2. Familial idiopathic basal ganglia calcification. Genetics Home Reference (GHR). February 2013; https://ghr.nlm.nih.gov/condition/familial-idiopathic-basal-ganglia-calcification.
            3. NINDS Fahr's Syndrome Information Page. National Institute of Neurological Disorders and Stroke (NINDS). February 13, 2007; https://www.ninds.nih.gov/disorders/fahrs/fahrs.htm. Accessed 9/4/2015.

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