Table 1.
Clinical and genetic data of the 24 probands
| P | Gene/variant | ACMG | AD/AR | Symptoms at onset (age) | Primary neurological symptom presumably related to BGC | Intracerebral calcifications (TCS, 0–80) | Number of bilateral locations with severe and confluent calcification (calcification score 5) | WMH intensity (0–3) | VRF |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Heterozygous SLC20A2 c.1240 G > T p.(Glu144*)[19] | LP, novel | AD | Cerebellar ataxia (SCA4, not related to BGCs) (25y) | Facial twitches | 10 | 1 | No hypodensities in the white matter (CT) | 0 |
| 2 | Heterozygous SLC20A2 c.1220C > A p.(Ser407*) | LP, novel | AD | Seizure (48y) | Personality changes, memory problems | 46 | 3 | 2 (MRI) | 0 |
| 3 | Heterozygous SLC20A2 c.1696A > T p.(Ile566Phe) | VUSa, novel | AD | TIA (40y) | Cognitive impairment | 60 | 6 | 3 (MRI) | 0 |
| 4 | Heterozygous SLC20A2 c.1703C > T p.(Pro568Leu) and heterozygous PDGFRB c.1808-6C > T | P/LP and VUS | AD | Anxiety (30y) | Hearing loss, anxiety, mild personality change | 40 | 3 | No hypodensities in the white matter (CT) | 0 |
| 5 | Heterozygous SLC20A2 c.1703C > T p.(Pro568Leu) | P/LP | AD | Mild cognitive impairment (60y) | Stroke (67y) | 8 | 0 | 3 (MRI) | 1 |
| 6 | Heterozygous PDGFB c.571C > T p.(Arg191*)[9] | LP | AD | Depression, Anxiety (14y) | Absence, seizure, TIAs (25y) | 4 | 0 | 2 (MRI) | 0 |
| 7 | Heterozygous PDGFB c.418C > T p.(Gln140*)[9] | LP | AD | Balance difficulties (64y) | Balance difficulties | 46 | 4 | 3 (MRI) | 0 |
| 8 | Homozygous MYORG c.1727G > A p.(Arg576His) | LP | AR | Gait/balance disturbance (41y) | Walking and speech difficulties | 73 | 7 | 3 (MRI) | 0 |
| 9 | Heterozygous MAP3K6 c.322G > A p.(Asp108Asn)[20] | LP | AD | Mild cognitive impairment (57y) | Mild cognitive impairment | 4 | 0 | 2 (MRI) | 1 |
| 10 | Heterozygous GLA c.394G > C p.(Gly132Arg) | P | AD | Gastric pain episodes (38y) | Stroke (47y) | 14 | 0 | 2 (MRI) | 0 |
| 11 | MT-TL1 m.3243A > C | P | Mit | Headaches/migraine (38y) | Headaches | 6 | 0 | 0 (MRI) | 2 |
| 12 | MT-TL1 m.3243A > C | P | Mit | Derealization, headaches (21y) | Headaches, depression episodes | 12 | 0 | 1 (MRI) | 1 |
| 13 | MT-TL1 m.3243A > C | P | Mit | Renal insufficiency and uncontrolled hypertension (23y) | Cognitive impairment | 20 | 1 | 2 (MRI) | 4 |
| 14 | MT-TL1 m.3243A > C | P | Mit | Ophthalmoplegia (35y) | Myopathy and fatigue | 8 | 0 | 1 (MRI) | 0 |
| 15 | Negative | Nd | Sporadic | TIA (57y) | Tremor | 4 | 0 | 1 (MRI) | 3 |
| 16 | Negative | Nd | Sporadic | Motor polyneuropathy (40y) | Motor polyneuropathy | 2 | 0 | Hypodensities in the white matter compatible with Fazekas 3 (CT) | 1 |
| 17 | Negative | Nd | AD | Parkinsonism (65y) | Parkinsonism | 4 | 0 | Hypodensities in the white matter compatible with Fazekas 1 (CT) | 2 |
| 18 | Negative | Nd | Sporadic | Headaches (24y) | Headaches/Parkinsonism | 4 | 0 | No hypodensities in the white matter (CT) | 0 |
| 19 | Negative | Nd | Sporadic | Essential tremor (45y) | Stroke (54y) | 48 | 4 | 2 (MRI) | 0 |
| 20 | Negative | Nd | Sporadic | Seizures (19y) | Walking difficulties | 34 | 2 | 2 (MRI) | 0 |
| 21 | Negative | Nd | Sporadic | Seizures (28y) | Seizures | 4 | 0 | 1 (MRI) | 0 |
| 22 | Negative | Nd | Sporadic | Balance disturbance (35y) | Balance difficulties, speech difficulties | 58 | 4 | 2 (MRI) | 0 |
| 23 | Negative | Nd | Sporadic | Balance disturbance, speech difficulties (32y) | Balance difficulties, speech difficulties | 2 | 0 | 1 (MRI) | 0 |
| 24 | Negative | Nd | Sporadic | Psychotic episodes (42y) | Seizures | 4 | 0 | 1 (MRI) | 0 |
ACMG American college of medical genetics, AD autosomal dominant, AR autosomal recessive, BGC basal ganglia calcifications, Nd not determined, LP likely pathogenic, Mit mitochondrial, P pathogenic, TCS total calcification score, TIA transitory ischemic attack, VUS variant of unknown significance, WMH white matter hyperintensities, VRF vascular risk factors: hypertension; diabetes; hyperlipidemia; heart disease or smoking, y years of age
asame variant also identified in son who had BGC and neurological symptoms, see Case Vignette in Results section