From variome to phenome: Pathogenesis, diagnosis and management of ectopic mineralization disorders

Table 6 Differential diagnosis of idiopathic basal ganglia calcification[116,140-143]

Disease	Distinct differences with IBGC
Basal ganglia calcification as incidental finding on CT scans/ aging	In 1% of CT scans Usually benign No clear etiology, especially when in older patients Asymptomatic
Hypoparathyroidism	Early onset: childhood/adolescence Hypoparathyroidism, hypocalcemia, hyperphosphatemia Alopecia, dry hair Dental dysplasia, caries Moniliasis Albright osteodystrophy symptoms (short stature, round facies, obesity, short metacarpals/metatarsals)
Pseudohypoparathyroidism (AD/maternal imprinting; GNAS, GNASAS1 and STX1A gene)	Early onset: childhood/adolescence Hyperparathyroidism, hypocalcemia, hyperphosphatemia Baseline cAMP in urine low; after Ellsworth Howard test subnormal Intellectual disability Albright osteodystrophy symptoms
Pseudo- pseudohypoparathyroidism (AD/paternal imprinting; GNAS gene)	Similar phenotype as pseudohypoparathyroidism Normal serum PTH, calcium and phosphorus Intellectual disability (more obvious than in PHP)
Kenny-Caffey syndrome, type 1 (AR; TBCE gene)	Growth delay Cortical thickening of long bones Hypocalcemia, hypoparathyroidism
PKAN (AR; PANK2 gene)	Early onset (10% > 10 yr) Pigmentary retinopathy
DRPLA (AD; CAG expansion in DRPLA gene)	Phenotype similar to IBGC
Neuroferritinopathy (AD; FTL gene)	Dysphagia
PLOSL (AR; TYROBP and TREM2 gene)	Radiography: polycystic osseous lesions Frontal lobe syndrome
Cockayne syndrome; Aicardi- Goutières syndrome	Onset in infancy/early childhood

AD: Autosomal dominant; AR: Autosomal recessive; CAG: Cytosine, adenine, guanine; cAMP: 3’-5’-cyclic adenosine monophosphate; CT: Computed tomography; DRPLA: Dentatorubropallidoluysian atrophy; FTL: Ferritin light chain; GNAS: GNAS complex locus; GNASAS1: GNAS complex locus, antisense transcript 1; IBGC: Idiopathic basal ganglia calcification; PANK2: Panthothenate kinase 2; PHP: Pseudohypoparathyroidism; PKAN: Panthothenate kinase-associated neurodegeneration; PLOSL: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy); PTH: Parathyroid hormone; STX1A: syntaxin 1A; TBCE: Tubulin-specific chaperone E; TREM2: Triggering receptor expressed on myeloid cells 2; TYROBP: Tyro protein tyrosine kinase-binding protein.