Clinical Diagnosis

The diagnosis of familial idiopathic basal ganglia calcification (FIBGC) is supported by the following criteria [modified from Moskowitz et al 1971, Ellie et al 1989, Manyam 2005]:

• Bilateral calcification of the basal ganglia visualized on neuroimaging. Other brain regions may also be affected. ^*
• Progressive neurologic dysfunction, generally including a movement disorder and/or neuropsychiatric manifestations. Age of onset is typically in the fourth or fifth decade, although this dysfunction may present in childhood or later in life.^*
• Absence of biochemical abnormalities and somatic features suggestive of a mitochondrial or metabolic disease or other systemic disorder
• Absence of an infectious, toxic, or traumatic cause
• Family history consistent with autosomal dominant inheritance

*Rarely, symptomatic individuals in families with FIBGC do not show calcification [Geschwind et al 1999]. Thus, in some instances, the diagnosis can be established in the absence of one (but not both) of the first two criteria, providing the remaining criteria are fulfilled.

Imaging studies

• Brain CT scan, which easily detects calcium, is the preferred method of localizing and assessing the extent of cerebral calcifications. Most frequently affected is the lenticular nucleus, especially the internal globus pallidus. Calcifications in the putamen, thalami, caudate, and dentate nuclei are common. Occasionally, calcifications begin or predominate in regions outside the basal ganglia. Calcification seems to be progressive, since calcifications are generally more extensive in older individuals and an increase in calcification can sometimes be documented on follow-up of affected subjects. (The calcifications in FIBGC are not distinguishable from those secondary to hypoparathyroidism or other causes.)
  
  Cerebellar gyri, the brain stem, centrum semiovale, and subcortical white matter may also be affected [Manyam et al 1992].
  
  Diffuse atrophic changes with dilatation of the subarachnoid space and/or ventricular system may coexist with calcifications.
• Magnetic resonance imaging (MRI). Calcified areas in the basal ganglia give a low-intensity signal on T2-weighted images and a low- or high-intensity signal on T1-weighted planes. In the cerebellum and cerebral white matter, the lesions may be more heterogeneous, sometimes seen as high signal on both T1 and T2, perhaps as a result of reactive gliosis or degenerating tissue within the calcified areas [Avrahami et al 1994].
• Plain skull radiograph. The calcifications appear as clusters of punctate densities symmetrically distributed above the sella turcica and lateral to the midline. Subcortical and cerebellar calcifications may appear wavy. Although the sensitivity of CT scan largely surpasses that of plain skull radiographs, the latter are still useful to evaluate abnormalities of bone structures suggestive of other diagnoses.

Testing

Normal findings include the following:

• Serum concentration of calcium, phosphorus, magnesium, alkaline phosphatase, calcitonin, and parathyroid hormone (PTH)
• Routine hematologic and biochemical investigations
• Workup for metabolic, inflammatory, and infectious conditions
• Ellsworth Howard test (i.e., a 10- to 20-fold increase of urinary cAMP excretion following stimulation with 200µ of PTH
• Cerebrospinal fluid evaluation for bacteria, viruses, and parasites; however, a slight increase in protein has been described [Boller et al 1977]

Neuropathology

• Gross pathologic examination shows accumulation of a granular material and solid nodules in the striatum, internal capsule, white matter, and cerebellum. Circumscribed calcium deposits may also be seen in the thalamus and cerebral cortex. Mild lobar atrophy is common.
• Histologic examination of affected areas shows concentric calcium deposits within the walls of small and medium-sized arteries and, less frequently, veins [Norman & Urich 1960, Cervos-Navarro & Urich 1995]. Droplet calcifications can be observed along capillaries. These deposits may eventually obliterate the lumina of vessels. The pallidal deposits stain positive for iron [Cervos-Navarro & Urich 1995]. Diffuse gliosis may surround the large deposits, but significant loss of nerve cells is rare.
• On electron microscopy, the mineral deposits appear as amorphous or crystalline material surrounded by a basal membrane. Calcium granules are seen within the cytoplasm of neuronal and glial cells.

Natural History

The clinical manifestations of familial idiopathic basal ganglia calcification (FIBGC) are limited to the nervous system. Most individuals with FIBGC are in good health during childhood and young adulthood. Typically, the age of onset is between 30 and 60 years of age with gradual progression of the movement disorder and neuropsychiatric symptoms.

Since the first description of familial idiopathic basal ganglia calcification (FIBGC) [Foley 1951], over 30 affected kindreds have been reported [Manyam et al 2001a].

The age at onset, clinical presentation, and severity of FIBGC are variable both between and within families. No correlation has been identified between age of onset, extent of calcium deposits, and neurologic deficits. In some instances, calcifications precede the clinical manifestations by several years [Manyam et al 1992]; in other instances, young symptomatic individuals with no changes observed on CT scan later develop radiologically visible calcification [Geschwind et al 1999].

The movement disorder often first manifests as clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping [Manyam et al 1992, Manyam et al 2001b]. Neurologic evaluation generally reveals an extrapyramidal syndrome with variable combination of bradykinesia, rigidity, festinating gait, hypophonia, mask-like facies, diminished blinking, dystonia, tremor, choreoathetosis, or dyskinesia. Palmomental and other frontal release signs may be elicited.

Pyramidal or cerebellar signs may also be present and, in some cases, the cerebellar picture predominates.

Dystonia is prominent in a few families [Larsen et al 1985].

Neuropsychiatric symptoms, often the first or most prominent manifestations, range from mild difficulty with concentration and memory to changes in personality or behavior to psychosis and dementia [Geschwind et al 1999, Benke et al 2004, Shakibai et al 2005]. It has been suggested that those who become symptomatic early in adulthood are more likely to have psychosis.

The pattern of dementia includes frequent frontal-executive dysfunction and resembles that occurring in other disorders affecting subcortical structures, including Wilson disease and Huntington disease [Geschwind et al 1999, Benke et al 2004, Modrego et al 2005, Weisman et al 2007].

Although premorbid psychomotor development is generally normal, low IQ and mild delay in motor or intellectual milestones during school age are described.

Other

• Seizures of various types occur frequently.
• Some individuals experience chronic headache [Geschwind et al 1999].
• Urinary urgency or incontinence and impotence may be present [Manyam et al 1992].
• Severe hypertension has been reported in two sisters with basal ganglia calcification with no other neurologic or systemic abnormalities; whether this represents a random association, a rare manifestation of FIBGC, or a distinct genetic disorder with basal ganglia calcification is unknown.
• General medical examination, growth, and facial appearance are normal. Strength and sensation are generally intact. Specifically, no abnormalities are detected in the skull, hands, teeth, nails, or skin, and there is no evidence of a parathyroid disorder.
• Neurophysiologic studies are generally normal.

Genotype-Phenotype Correlations

Only one kindred with linkage to the IBGC1 locus has been identified to date; the associated gene is unknown. The clinical presentation of the family with IBGC1 does not differ significantly from other FIBGC kindreds reported in the literature.

Penetrance

Although penetrance may vary among and within families, analysis of reported pedigrees indicates about 95% penetrance by age 50 years or older.

No reliable correlations exist between age of onset, extent of calcium deposits, and neurologic deficit. Although most individuals with calcifications eventually develop neurologic dysfunction, the type or severity of clinical symptoms cannot be predicted from the pattern of calcification.

Anticipation

Anticipation was observed in one family with FIBGC [Geschwind et al 1999].

Nomenclature

FIBGC is the preferred term for this condition. Manyam [2005] lists 35 different names used in the literature for this condition.

Although the term Fahr's disease is often used to designate either familial idiopathic basal ganglia calcification or idiopathic basal ganglia calcification without a positive family history, it is unknown whether the nonfamilial cases represent FIBGC. The term Fahr's disease is ambiguous and should be avoided.

Prevalence

The prevalence of FIBGC is unknown; about 30 kindreds have been reported. However, the disorder is probably under-recognized because of insufficient investigation of other family members of individuals presenting with calcification of the basal ganglia.

Parathyroid Disorders

Hypoparathyroidism (HP), idiopathic or postsurgical, is the most common cause of symmetric calcification of the basal ganglia [Illum & Dupont 1985]. Hypoparathyroidism usually begins in childhood or adolescence (i.e., earlier than is observed in FIBGC). In individuals with hypoparathyroidism, decreased serum concentration of PTH results in hypocalcemia and hyperphosphatemia and their clinical manifestations (i.e., tetany, muscle weakness, paresthesias, seizures, and intellectual disability). Additional features include cataracts, dry hair, alopecia, dental dysplasia, caries, and predisposition to moniliasis. Because treatment of HP may lead to marked clinical improvement, it is appropriate to evaluate individuals with calcification of the basal ganglia for hypoparathyroidism.

Pseudohypoparathyroidism (PHP) and pseudo-pseudohypoparathyroidism (PPHP) are the phenotypic spectrum caused by mutations in GNAS, encoding the alpha subunit of a G-protein, which is involved in signal transduction. Molecular genetic testing of GNAS is clinically available. PHP and PPHP can occur in the same family. Occasionally, variants of PHP (types IB and II) or PPHP may have few or no somatic abnormalities, making diagnosis on clinical grounds difficult.

PHP results from end-organ unresponsiveness to PTH. The biochemical hallmarks are hypocalcemia and hyperphosphatemia with an elevated serum concentration of PTH. The baseline rate of excretion of urinary cAMP is below normal; after infusion of exogenous PTH, the increase in urinary excretion of phosphate and cAMP is generally subnormal. PHP type II is a variant of PHP with normal cAMP response; cases of PHP have also been reported with normal serum calcium concentration.

The average age of onset of PHP is eight to ten years. Most clinical manifestations are related to hypocalcemia and thus similar to those in hypoparathyroidism, with intellectual disability being somewhat more common in PHP. Affected individuals may have other manifestations of Albright hereditary osteodystrophy, including short stature, round facies, obesity, soft tissue calcification, short metacarpals or metatarsals, and other hormone resistance, resulting in hypothyroidism and/or hypogonadism.

PPHP, in contrast, is characterized by the physical findings of Albright hereditary osteodystrophy with normal serum concentration of calcium and phosphorus and normal response to PTH stimulation.

Kenny-Caffey syndrome type 1, characterized by growth delay, cortical thickening of the long bones, hypocalcemia, hypoparathyroidism, and calcification of the basal ganglia, is caused by mutations in TBCE, the gene encoding a chaperone protein required for proper folding of alpha-tubulin subunits and the formation of alpha-beta-tubulin heterodimers [Parvari et al 2002]. Inheritance is autosomal recessive.

Mitochondrial Disorders

Mineral deposits in the basal ganglia and other brain structures are observed in mitochondrial diseases (see Mitochondrial Disorders Overview). Some mitochondrial disorders only affect a single organ (such as the eye in Leber hereditary optic neuropathy), but many involve multiple organ systems and often present with prominent neurologic and myopathic features. Many individuals with mitochondrial abnormalities have a discrete clinical syndrome such as Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged-red fibers (MERRF), neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS). However, clinical variability is considerable and many do not fit neatly into a recognized syndrome.

Infectious Diseases

Intrauterine or perinatal infection with toxoplasmosis, rubella, cytomegalovirus, or herpes simplex virus may result in calcification of the basal ganglia and dentate nucleus, as well as irregular masses of calcium distributed throughout the brain. CNS infection should be considered when clinical onset occurs soon after birth, especially in the presence of chorioretinitis, microcephaly, or neurologic abnormalities.

Non-congenital, active viral encephalitis should also be considered in some individuals with brain calcifications and negative family history [Morita et al 1998]. In AIDS, either opportunistic infections or inflammatory changes may cause symmetric calcified lesions in the basal ganglia, mostly in children.

Bacterial or parasitic infections such as brucellosis, toxoplasmosis, or cysticercosis should be considered, although the appearance and distribution of calcific deposits are generally quite different in FIBGC.

• Brucellosis. Although cerebral calcification is rare, the detection of basal ganglia calcification in individuals residing in endemic areas should raise the possibility of CNS brucellar infection.
• Toxoplasmosis. The basal ganglia are affected in up to 75% of cases.
• Parenquimatous cysticercosis. Calcifications are a manifestation of death of the larvae and are generally rounded, less symmetrical, and scattered within the grey matter or grey-white matter junction, sometimes in the basal ganglia or in the deep matter. This diagnostic possibility should be borne in mind in regions in which cysticercal infection is common. MRI is more sensitive than CT scan in identifying the parasitic cysts.

Adult-Onset Neurodegenerative Conditions

Neurodegeneration with brain iron accumulation (NBIA) disorders

• Pantothenate kinase-associated neurodegeneration (PKAN) is a form of NBIA (formerly called Hallervorden-Spatz syndrome). PKAN is characterized by progressive dystonia and basal ganglia iron deposition with onset that usually occurs before age ten years. Commonly associated features include dysarthria, rigidity, and pigmentary retinopathy. About 25% of affected individuals have an 'atypical' presentation with later onset (after age ten years), prominent speech defects, psychiatric disturbances, and more gradual progression of disease. Approximately 50% of individuals given a clinical diagnosis of NBIA have identifiable mutations in PANK2. To date, all individuals with NBIA who are found to have the 'eye-of-the-tiger' sign on T₂-weighted magnetic resonance imaging have been found to have at least one mutation in PANK2. Inheritance is autosomal recessive.
• Neuroferritinopathy, a form of NBIA, typically presents with progressive adult-onset chorea or dystonia and subtle cognitive deficits. The movement disorder involves additional limbs within five to ten years and becomes more generalized within 20 years. Cognitive deficits, behavioral issues, and dysphagia become major problems with time. The diagnosis of neuroferritinopathy is based on clinical findings, including adult-onset chorea or dystonia and MRI or CT showing excess iron storage or cystic degeneration in the putamina. FTL is the only gene currently known to be associated with neuroferritinopathy. Inheritance is autosomal dominant.

Dentatorubro-pallidoluysian atrophy (DRPLA). Bilateral calcification of the globus pallidus has also been reported in individuals with the allelic variant of DRPLA, the Haw-River syndrome, a neurodegenerative disorder described in a large African-American family from North Carolina. Affected individuals show a varied combination of gait ataxia, dysarthria, involuntary movements, seizures, psychosis, and dementia, overlapping with the clinical picture of families with FIBGC. The diagnosis of DRPLA rests on positive family history, characteristic clinical findings, and the detection of an expansion of a CAG/polyglutamine tract in the DRPLA gene.

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is characterized by fractures resulting from radiologically demonstrable polycystic osseous lesions, frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade. Bilateral calcifications of the basal ganglia, most often in the putamina, are commonly observed on CT. Calcifications may occur before CNS symptoms appear. TYROBP (DAP12) and TREM2 are the two genes associated with PLOSL. Inheritance is autosomal recessive.

Autosomal dominant dystonia-plus syndrome with brain calcinosis. Baba et al [2005] have updated information on a family with FIBGC associated with movement disorders (dystonia, chorea, ataxia), mean age of onset of 19 years, and no linkage to 14q.

Inherited Congenital or Early-Onset Syndromes

Calcifications in the basal ganglia and other brain structures are encountered in several congenital or early-onset syndromes with normal calcium-phosphorus metabolism and frequently associated intellectual disability.

Cockayne syndrome (CS) includes several forms that differ by age of onset:

• CS type I (the "classic" form) presents with growth and developmental delays in the first two years of life. Progressive impairment of vision, hearing, and central and peripheral nervous system function lead to severe disability, with death typically occurring in the first or second decade. Intracranial calcifications, including of the basal ganglia, are seen in some individuals.
• CS type II, a more severe form, also known as "connatal" Cockayne syndrome, cerebro-oculo-facial syndrome (COFS), or Pena-Shokeir type II syndrome, exhibits growth failure at birth with little or no postnatal neurologic development, congenital cataracts and other structural eye anomalies, kyphosis/scoliosis and joint contractures, and death usually by age seven years.
• CS type III is a milder, rare form with late onset.

Cockayne syndrome is diagnosed in classic cases by clinical findings and in "non-classic" cases by assay of DNA repair in skin fibroblasts or lymphoblasts. Mutation in two genes, ERCC6 and CKN1, is causative. Inheritance is autosomal recessive.

Aicardi-Goutières syndrome is an early-onset encephalopathy characterized by mental and physical handicap associated with calcificiation of the basal ganglia, particularly the putamen, globus pallidus, and thalamus; leukodystrophy; cerebral atrophy; chronic cerebrospinal fluid (CSF) leukocytosis; and increased concentration of interferon-alpha in the CSF. Onset typically occurs in the first three months of life; normal initial development is followed by loss of acquired skills, progressive microcephaly, irritability, feeding problems, sterile pyrexias, and hypersomnia. About 20%-25% of individuals have generalized tonic-clonic or focal tonic seizures. Four associated genes, RNASEH2A, RNASEH2B, RNASEH2C, and TREX1, have been identified. Inheritance is autosomal recessive.

Tuberous sclerosis complex involves abnormalites of the skin (hypomelanotic macules, facial angiofibromas, shagreen patches, fibrous facial plaques, ungual fibromas), brain (cortical tubers, subependymal nodules, seizures, intellectual disability/developmental delay), kidney (angiomyolipomas, cysts), and heart (rhabdomyomas, arrhythmias). The cerebral hamartomas may be calcified; however, they are mainly periventricular or subcortical. Two associated genes, TSC1 and TSC2, have been identified. Inheritance is autosomal dominant.

Down syndrome. Reports of basal ganglia calcifications in Down syndrome are abundant.

Other

Calcifications of the basal ganglia may result from the following:

• Necrosis of neural tissue caused by traumatic, toxic, or physical insults. These include but are not limited to perinatal anoxia, Rh incompatibility, carbon monoxide intoxication, mercury and lead poisoning, exposure to ionizing radiation, and methotrexate therapy.
• Systemic lupus erythematosus (SLE)
• Celiac disease. Although intracranial calcifications have been described, the calcium deposits are mainly occipital. Other neurologic manifestations can include cerebellar ataxia, epilepsy, and peripheral neuropathy.
• Normal aging. Calcification of the basal ganglia is an incidental finding in about 0.3%-1.5% of brain CT scans, especially in aged individuals (age therefore being the most common cause). Microscopic calcifications can be observed in the globus pallidus and dentate nucleus in up to 70% of autopsy series. These calcifications are generally confined to the globus pallidus and do not have associated clinical findings [Forstl et al 1992]. Basal ganglia calcifications in the aged have been associated with psychotic symptoms [Ostling et al 2003].

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with familial idiopathic basal ganglia calcification (FIBGC), thorough neurologic and neuropsychiatric assessment is recommended.

Treatment of Manifestations

The following are appropriate:

• Pharmacologic treatment to improve anxiety, depression, and obsessive-compulsive behaviors
• To alleviate dystonia and other associated involuntary movements, pharmacologic therapies as typically used in neurologic practice for the treatment of movement disorders
• Oxybutynin for urinary incontinence
• Appropriate antiepileptic drugs (AEDs) for seizures

Surveillance

Thorough neurologic and neuropsychiatric assessment is indicated annually.

Agents/Circumstances to Avoid

Neuroleptic medication should be used cautiously, since it may exacerbate extrapyramidal symptoms [Cummings et al 1983]. A poor response to neuroleptics was obtained in a family with FIBGC and mainly psychotic manifestations [Callender 1995].

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Anecdotally, a therapeutic trial with sodium etidronate in one affected individual resulted in partial improvement of speech and gait, but not other neurologic symptoms; no reduction in the amount of calcification was observed [Loeb 1998].

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.

Other

The response of parkinsonian features to levodopa therapy is generally poor; however, Manyam et al [2001a] attributed a positive response to levodopa in an affected individual in a family with FIBGC to the coexistence of IBGC and idiopathic Parkinson disease.

Genetics clinics, staffed by genetics professionals, provide information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.

Mode of Inheritance

Familial idiopathic basal ganglia calcification (FIBGC) is inherited in an autosomal dominant manner.

Risk to Family Members

This section is written from the perspective that molecular genetic testing for this disorder is available on a research basis only and results should not be used for clinical purposes. This perspective may not apply to families using custom mutation analysis.— ED.

Parents of a proband

• Most individuals diagnosed with FIBGC have an affected parent as identified either clinically or by brain CT scan. However, the transmitting parent may be clinically asymptomatic or may develop disease manifestations that are later in onset or less severe than those in the proband.
• A proband with FIBGC may have the disorder as the result of a de novo gene mutation. The proportion of cases caused by de novo mutations is unknown. Whether nonfamilial (simplex) cases represent de novo gene mutations (thus placing their children at a 50% risk) or non-genetic conditions is also not known.
• Recommendations for the evaluation of parents of a proband with an apparent de novo mutation include physical and neurologic examination and CT scan.

Note: Although most individuals diagnosed with FIBGC have an affected parent, the family history may appear to be negative because of failure to recognize the disorder in family members, early death of the parent before the onset of symptoms, or late onset of the disease in the affected parent.

Sibs of a proband

• The risk to the sibs of a proband depends on the genetic status of the parents.
• If one parent is affected, the sibs of the proband are at a 50% risk of being affected.
• When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low and depends on the spontaneous mutation rate of the gene(s) involved and the probability of germline mosaicism in a parent, both of which are currently unknown.

Offspring of a proband. Each child of an individual with FIBGC has a 50% chance of inheriting the mutation.

Other family members. The risk to other family members depends on the genetic status of the proband's parents. If a parent is affected, his or her family members are at risk.

Related Genetic Counseling Issues

Family planning. The optimal time for determination of genetic risk is before pregnancy.

Testing of at-risk asymptomatic adults. Since calcium deposits may precede the onset of clinical symptoms by several years, a brain CT scan serves as a presymptomatic test in at-risk individuals. Thus, psychological and ethical considerations in offering such testing should be similar to those applied for other neurodegenerative disorders in which a curative treatment is not currently available, including the caveat regarding testing of at-risk individuals who are younger than 18 years of age.

Brain CT scan is not useful in predicting age of onset, severity or type of symptoms, or rate of progression in asymptomatic individuals. Testing for calcium deposits using brain CT scan in the absence of definite symptoms of the disease is predictive testing. At-risk asymptomatic adult family members may seek testing in order to make personal decisions regarding reproduction, financial matters, and career planning. Others may have different motivations including simply the "need to know." Testing of asymptomatic at-risk adult family members usually involves pre-test interviews in which the motives for requesting the test, the individual's knowledge of FIBGC, the possible impact of positive and negative test results, and neurologic status are assessed. Those seeking testing should be counseled about possible problems that they may encounter with regard to health, life, and disability insurance coverage, employment and educational discrimination, and changes in social and family interaction. Other issues to consider are implications for the at-risk status of other family members. Informed consent (including the possibility of incidental findings on a CT scan and whether such findings will be discussed) should be procured and records kept confidential. Individuals with a positive test result need arrangements for long-term follow-up and evaluations.

Testing of at-risk asymptomatic individuals during childhood. Consensus holds that individuals younger than age 18 years who are at risk for adult-onset disorders for which no treatment exists should not be tested in the absence of symptoms. The principal arguments against testing asymptomatic individuals under age 18 years for FIBGC are that such testing removes the individual's future autonomy to make his/her own medical decisions and, because no treatment is currently available, it has no immediate medical benefit. Furthermore, a CT scan will not remove uncertainty in the case of FIBGC because penetrance is age dependent, reaching about 95% by age 50 years.

In addition, testing of individuals during childhood runs the risk of causing psychological harm to the child by altering self-image, disturbing parent-child or sibling-sibling relationships, increasing anxiety and guilt, and stigmatizing the child. Moreover, the child could be discriminated against as an adult through denial of health insurance coverage.

Symptomatic individuals who are younger than age 18 years who are tested usually benefit from having a specific diagnosis established. See also the National Society of Genetic Counselors Position statement on genetic testing of minors for adult-onset conditions and the American Society of Human Genetics and American College of Medical Genetics Points to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents.

A normal brain CT scan does not completely eliminate the possibility of FIBGC, especially in younger individuals.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. See for a list of laboratories offering DNA banking.

Prenatal Testing

Because the gene(s) in which mutations causing FIBGC occur are unknown, and linkage analysis is available on a research basis only, prenatal diagnosis for FIBGG is not available.

Published Guidelines/Consensus Statements

1. American Society of Human Genetics and American College of Medical Genetics. Points to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents. Available online. 1995. Accessed 3-1-13. [PMC free article: PMC1801355] [PubMed: 7485175]
2. National Society of Genetic Counselors. Position statement on genetic testing of minors for adult-onset disorders. Available online. 2012. Accessed 3-1-13.

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Revision History

• 20 September 2007 (me) Comprehensive update posted to live Web site
• 9 June 2004 (me) Comprehensive update posted to live Web site
• 18 April 2002 (me) Review posted to live Web site
• 28 September 2001 (ms) Original submission