Skip to main content

Table 1 Monogenic disorders associated with cerebral small vessel disease (modified from Bersano et al. [7])

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
  1. CADASIL cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CARASIL cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, RVCL retinal vasculopathy with cerebral leukodystrophy