Table 1.
Monogenic Disorders Associated with Cerebrovascular Disease
| Syndrome | Inheritance | Gene | Chromosome region | Symptoms | Vascular pathology |
|---|---|---|---|---|---|
| CADASIL | AD | NOTCH3 | 19p13.1 | Migraine, cognitive problems, depression, seizures, stroke | Small-vessel vasculopathy |
| CARASIL | AR | HTRA1 | 10q | Spasticity, stroke, cognitive problems, scalp hair loss, back pain | |
| MELAS | Maternal | MTTL1 | mtDNA | Muscle weakness, headache episodes, seizures, strokelike episodes | |
| Fabry disease | XL-R | GLA | Xq22 | Episodes of pain in hands and feet, angiokeratomas, corneal opacity, renal affection, heart affection, stroke | Small and large artery vasculopathy |
|
MYMY1
MYMY2 MYMY3 MYMY4 MYMY5 |
AD? AD? AD? XL-R AD |
n.d.
RNF213 n.d. BRCA1/2-containing complex, subunit 3 MTCP1/MTCP1NB ACTA2 |
3p24.2-p26 17q25.3 8q23 Xq28 Xq28 10q23.31 |
Progressive, occlusive, cerebrovascular arteriopathy, bilateral progressive stenosis of the distal internal carotid arteries, with particular involvement of the circle of Willis | Large-artery vasculopathy |
| Marfan syndrome type 1 and 2 | AD | FBN1, TGFBR2 | 15q21.1-3p24.1 | Tall build, long arms, legs, scoliosis, flat feet, fatigue, shortness of breath, heart palpitations, chest pain, partial lens dislocation, spontaneous pneumothorax | Arterial dissection |
| Hereditary cerebral hemorrhage with amyloidosis of the Dutch type | AD | APP | 21q21.3 | Lobar intracerebral hemorrhage, cerebral microbleeds, cognitive problems | Inherited cerebral amyloid angiopathies |
| Cystatin C-related familial cerebral amyloid angiopathy | AD | CST3 | 20p11.21 | Intracerebral haemorrhage, stroke and dementia | |
| Transthyretin-related CAA | AD | TTR | 18q12.1 | Pain, paresthesia, muscular weakness, autonomic dysfunction, sensory and motor polyneuropathy | |
| Autosomal dominant polycystic kidney disease adult type I and II | AD | PDK1, PDK2 | 16p13.3-4q22.1 | Pain in the abdomen, side or lower backhaematuria, hypertension, kidney stones recurrent urinary tract infections, loss of kidney function | Cerebrovascular malformations |
| Cerebral cavernous malformations | AD | KRIT1, C7orf22, PDCD10 | 7q21-q22, 7p13-p15, 3q25.2-q27 | Some are silent, others cause seizures, hemorrhage, or focal neurologic deficit | |
| Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) | AD | ENG, ACVRL1 | 9q34.1, 12q11-q14 | Telangiactasia, arteriovenous malformations in lungs, brain, liver, intestines, intracerebral hemorrhage, ischemic stroke |
AD: Autosomal dominant; AR: Autosomal recessive; CAA: Cerebral amyloid angiopathy; CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASIL: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; MELAS: Mitochondrial encephalomyopathy, lactic acidosis and stroke episodes; MYMY: Moyamoya disease; n.d.: Not determined; XL-R: X-linked recessive. NOTCH3: Neurogenic locus notch homolog protein 3; HTRA1: Serine protease HTRA1; MTTL1: Mitochondrially encoded tRNA leucine 1; GLA: Alpha-galactosidase; RNF213: Ring finger protein 213; BRCA1/2: Breast cancer 1/2; MTCP1/MTCP1NB: Mature T-cell proliferation 1 and mature T-cell proliferation 1 neighbor; ACTA2: Alpha-actin-2; FBN1: Fibrillin-1; TGFBR2: Transforming growth factor, beta receptor II; APP: Amyloid precursor protein; CST3: Cystatin C or cystatin 3; TTR: Transthyretin; PDK1 and PDK2: Pyruvate dehydrogenase lipoamide kinase isozyme 1 and 2; KRIT1: Krev interaction trapped protein 1; C7orf22: Malcavernin; PDCD10: Programmed cell death protein 10; ENG: Endoglin; ACVRL1: Activin A Receptor Type II-Like 1.