Idiopathic basal ganglia calcification-4 is an autosomal dominant condition characterized by the accumulation of calcium deposits in various brain regions, most commonly in the basal ganglia. About half of mutation carriers are asymptomatic, but some present later in ... Idiopathic basal ganglia calcification-4 is an autosomal dominant condition characterized by the accumulation of calcium deposits in various brain regions, most commonly in the basal ganglia. About half of mutation carriers are asymptomatic, but some present later in life with parkinsonism and impaired cognitive function. Migraine or depression may occur in younger individuals (summary by Nicolas et al., 2013). For a detailed phenotypic description and a discussion of genetic heterogeneity of IBGC, see IBGC1 (213600).
Nicolas et al. (2013) reported a large 3-generation French family in which multiple members had basal ganglia calcifications apparent on brain imaging. The proband was a woman in the oldest generation who presented at age 54 years with ... Nicolas et al. (2013) reported a large 3-generation French family in which multiple members had basal ganglia calcifications apparent on brain imaging. The proband was a woman in the oldest generation who presented at age 54 years with asymmetric parkinsonism with a good response to levodopa. Medical history revealed that she was diagnosed with bipolar disorder at age 20 years. At age 65 years, she showed cognitive impairment with dysexecutive syndrome and memory difficulties, which progressed to dementia. Brain CT showed strio-pallido-thalamo-dentate calcifications, with periventricular and juxtacortical hyperintensities on MRI. Brain imaging of 12 other relatives showed basal ganglia calcifications, although most were clinically asymptomatic. One patient had severe personality disorder, nystagmus, and suicide attempts, and died at age 34 years. The 6-year-old child of this patient had calcifications and attention deficit-hyperactivity disorder and migraine. Two others had migraine with aura. Six mutation carriers were asymptomatic, including 2 individuals in their sixties. An unrelated woman with the disorder presented at age 66 years with a cognitive dysexecutive disorder. Physical examination showed bradykinesia and pyramidal signs without rigidity. Brain imaging showed basal ganglia calcifications and periventricular and subcortical abnormalities on MRI.
In affected members of a large 3-generation family with idiopathic basal ganglia calcification-4, Nicolas et al. (2013) identified a heterozygous mutation in the PDGFRB gene (L658P; 173410.0001). The mutation, which was identified by exome sequencing of 2 affected ... In affected members of a large 3-generation family with idiopathic basal ganglia calcification-4, Nicolas et al. (2013) identified a heterozygous mutation in the PDGFRB gene (L658P; 173410.0001). The mutation, which was identified by exome sequencing of 2 affected individuals and confirmed by Sanger sequencing, segregated with the disorder in this family and was not found in several large exome databases. Sequencing of the PDGRFB gene in 10 other affected families and 9 patients with apparently sporadic disease revealed 1 adult with a heterozygous mutation (173410.0002) and no family history. Nicolas et al. (2013) noted that animal models have shown a key role for Pdgfrb in the development of pericytes in vessels within the brain, and that pericytes have a key role in maintaining the integrity of the blood-brain barrier, which is hypothesized to be impaired in IBGC. In addition, the PDGFB-PDGFRB pathway appears to be involved in phosphate-induced calcifications in vascular smooth muscle cells by modulating expression of the phosphate transporter SLC20A1 (137570) (Villa-Bellosta et al., 2009); IGBC3 (614540) is caused by mutation in a related phosphate transporter SLC20A2 (158378). These findings suggest that cerebral phosphate homeostasis may play a role in vascular calcifications.