From: Genetics of vascular dementia – review from the ICVD working group
Disease | CADASIL | Fabry disease | RVCL | COL4A1 | CARASIL |
---|---|---|---|---|---|
OMIM | #125310 | #301500 | #192315 | #120130 | #60142 |
Pattern of inheritance | Autosomal dominant | X-linked recessive | Autosomal dominant | Autosomal dominant | Autosomal recessive |
Gene | NOTCH3 | α-GAL A gene (GLA) | TREX1 | COL4A1 | HTRA1 |
Locus | 19p13 | Xq22 | 3p21.3-p21.2 | 13q34 | 10q25 |
Gene product | Notch 3 receptor | Alpha galactosidase A enzyme | DNA specific 3’-5’ exonuclease DNase III | Type IV collagen α1 | HTRA1 serine peptidase/protease 1 |
Clinical manifestations | |||||
Stroke | |||||
Age at onset, years | 20–70 | 33–46 (M)/40–52 (F) | 40–50 | 14–49 | 20–40 |
Stroke subtype | |||||
Small vessel disease | + | + | + | + | + |
Large vessel disease | – | + | – | – | – |
Cardioembolic | – | + | – | – | – |
Hemorrhagic | Rare | Rare | – | + | – |
Other neurological manifestations | |||||
Psychiatric disturbance | + | + | + | + | + |
Migraine with/without aura | + | – | + | + | – |
Seizures | + | + | + | ||
Cognitive impairment | + | ± | + | + | + |
Extra-neurological manifestations | |||||
Neuropathy | – | + (80%) | ± | + | – |
Myopathy | – | – | + | + | + |
Renal disease | – | + | + | + | – |
Skin involvement | – | + | – | – | – |
Ocular involvement | ± Retinal arteriolar narrowing | + Cornea verticillata | + Retinopathy | + Cataracts, retinopathy | + Retinopathy |
Gastrointestinal involvement | – | + | ± | + | – |
Cardiac involvement | – | + | – | + | – |
Others | Acroparhestesia, hypoacusia | Raynaud phenomena (80%), hepatopathy | Poroencephaly, prenatal bleeding, infantile hemiparesis | Alopecia, spondylosis deformans, acute lumbago | |
Radiological findings | |||||
White matter lesions | + | + | + | + | + |
Lacunar lesions | + | + | + | + | + |
Cortical-subcortical lesions | – | + | ± | – | – |
Intracerebral hemorrhage (ICH) | + | + | – | + | + |
Aneurysms | – | + | – | + | – |
Peculiar findings | Temporal lobe hyperintensities, external capsule involvement | Pulvinar hyperintensities on T1-wheighted images | Subcortical contrast-enhancing lesions with surrounding edema | Porencephaly, ICH | – |
Pathological findings | Granular osmiophilic material surrounding vascular smooth muscle cells | Cytoplasmatic Gb3 inclusions in vascular endothelial cells and smooth muscle cells | Multilaminated vascular basement membranes | Interruption and thickening of basement membrane | Degeneration in vascular smooth muscle cells |