Familial idiopathic basal ganglia calcification (Fahr's disease) without neurological, cognitive and psychiatric symptoms is not linked to the IBGC1 locus on chromosome 14q

Abstract

Idiopathic basal ganglia calcification (IBGC) is characterised by radiological, neurological, cognitive and psychiatric abnormalities. The associations between these abnormal phenotypes and abnormal genes remain unclear despite the recent mapping to chromosome 14q of a susceptibility locus for IBGC ( IBGC1). We identified two siblings, from a large multigenerational pedigree, who had both been diagnosed with radiological IBGC, dementia, bipolar affective disorder and Parkinsonism. We assessed (1) other family members to determine whether these four phenotypes were co-segregating as symptoms of IBGC, and (2) possible IBGC linkage to the IBGC1 locus on chromosome 14q or to any known or potential dementia genes. Nine second-generation and 21 third-generation members received radiological, neurological, neuropsychological and psychiatric assessments. We genotyped all family members for microsatellite markers at the IBGC1 locus and polymorphisms of the ApoE, VLDL, alpha1-ACT, BChE-K, APP, PS1, PS2 and tau genes and tested these for linkage to IBGC, dementia and bipolar disorder. Of the ten family members with radiological intracranial calcification, all except the two index cases were normal. There was no significant association between IBGC status and severe cognitive impairment or dementia ( P=0.335) or bipolar affective disorder or Parkinsonism ( P=1.0). Linkage to the IBGC1 locus was excluded. Of the eight dementia gene markers tested, the only positive LOD score was for the ApoE epsilon4 polymorphism and dementia/severe cognitive impairment. We have identified a form of IBGC in which calcification is inherited independently of neurological, cognitive and psychiatric symptoms. This may represent a second locus for this disorder.

Fahr's Disease: An Uncommon Cause of Intracranial Calcification in Children

“…There is no reliable correlation between age, extent of calcium deposits in the brain, and neurological defi cit. Since the appearance of calcifi cation is age-dependent, a CT scan could be negative in a gene carrier who is younger than the age of 55 2,3 . Genetic analysis could not be done due to lack of facility for the same in our set up.…”

“…Genetic analysis could not be done due to lack of facility for the same in our set up. Idiopathic Fahr's disease has been linked to IBGC1 locus on chromosome 14q in some cases 2,3 . However research is needed to understand the actions of the genes involved in this disorder.…”

“…I diopathic bilateral striopallidodentate calcifi cation or Fahr's disease is a degenerative disease normally found in the [5][6] th decade of life with autosomal dominant inheritance 1,2,3,4 . Few sporadic cases are reported.…”

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“…However additional areas of calcification are putamen, caudate nucleus, internal capsule, dentate nucleus, thalamus, cerebellum and cerebral white matter. The calcium deposits occur in the extracellular and extravascular space often surrounding the capillaries [6,7]. It has been suggested that tissue damage by free radicals or by abnormal iron transportation may trigger the calcification [8].…”

Fahr’s syndrome and clinical correlation: a case series and literature review

“…There are no biochemical abnormalities and clinical features suggesting the presence of mitochondrial, metabolic disease or other systemic disorders; calcifications are not due to infection, trauma, or toxic causes; moreover, autosomal dominant inheritance (chromosome 14q9) for basal ganglia calcification has been discovered [17] (Table I). Brodaty et al [7] excluded such a locus in the absence of neurological, cognitive and psychiatric symptoms. Further, in hypothyroidism the locus is on 11p [24]; in pseudohypoparathyroidism it is on 20q [37]; in Down's syndrome it is on 21q [48], excluding the possibility that a single gene may be responsible for the calcium and other mineral deposits.…”