Table 3: Summary of the most important connective tissue diseases related to stroke in young adults.

DiseaseInherit.DiagnosisPhenotype

Vascular Ehlers-Danlos syndromeADBiochemical analysis (skin biopsy)
COL3A1 analysis (fibroblasts)
Facial gestalt (thin nose and lips, sunken cheeks), skin fragility, extreme vascular fragility, rupture of uterus and colon
Intracerebral aneurysm, carotid/vertebral dissection
Type 4 collagen-related small vessel diseaseADCOL4A1 analysis (blood sample)Infantile hemiparesis, seizures, migraine, retinal artery tortuosity, renal and muscular involvement
Small vessel ischaemic stroke or haemorrhage
HANAC syndromeADSkin biopsy
COL4A1 analysis (blood sample)
Hereditary angiopathy with retinal artery tortuosity, cystic renal disease, cerebral aneurysm, muscle cramps
Osteogenesis imperfectaAD
AR
Radiological examination
Biochemical analysis (skin biopsy)
Molecular analysis of OI genes (fibroblasts and blood sample)
Fractures, osteopenia, bone deformities, hearing loss, blue sclerae, dentinogenesis imperfecta
Intracerebral aneurysm, moyamoya-like disease, carotid/vertebral dissection
AD polycystic kidneysADRenal ultrasonography
PKD1/2 linkage analysis (blood)
PKD1/2 molecular analysis (blood)
Bilateral renal cysts, liver and pancreas cysts, aortic dilatation/dissection
Intracranial aneurysm
Pseudoxanthoma elasticumARSkin biopsy
ABCC6 analysis (blood sample)
Yellowish skin papules in flexural areas, retinopathy, coronary and peripheral artery disease
Ischaemic stroke in patients and heterozygous carriers
PXE-like syndromeARCoagulation testing
Skin biopsy
GGCX analysis (blood sample)
Generalized cutis laxa, mild retinopathy, coagulation disorder
Cerebral aneurysm?
Marfan syndromeADRevised Ghent Nosology
Fibrillin 1 analysis (blood sample)
Tall stature, arachnodactyly, pectus deformity, ectopia lentis, aortic root dilatation
Carotid artery dissection, cerebral and spinal cord infarction
Loeys-Dietz syndrome Type IADTGFBR1 and 2 analysis (blood sample)Marfanoid habitus, hypertelorism, cleft palate, bifid uvula, generalized arterial tortuosity and aneurysms
intracranial aneurysm, carotid and vertebral aneurysm
Loeys-Dietz syndrome Type IIADTGFBR1 and 2 analysis (blood sample)Vascular EDS-like phenotype, generalized arterial tortuosity and aneurysms
intracranial aneurysm, carotid and vertebral aneurysm
Bicuspid aortic valveADEchocardiography
NOTCH1 gene in familial cases (blood sample)
Bicuspid aortic valve on ultrasound
Dissection of carotid and cerebral arteries, intracranial aneurysm
Arterial tortuosity syndromeARSLC2A10 analysis (blood sample)Facial dysmorphism, arachnodactyly, joint and skin laxity, arterial elongation, tortuosity and aneurysms
Ischaemic stroke?
Supravalvular aortic stenosisADELN analysis (blood sample)Left ventricular outflow obstruction
Ischaemic stroke
Williams-Beuren syndromeADFISH or microarraySVAS, facial dysmorphism, short stature
Ischaemic stroke, intracerebral haemorrhage
Spontaneous cervical artery dissectionADClinical examinationExclude vascular EDS, Marfan syndrome and osteogenesis imperfecta
Hereditary haemorrhagic telangiectasiaADClinical evaluation
ENG and ALK1 analysis (blood sample)
Mucocutaneous telangiectases, epistaxis, gastrointestinal haemorrhage
Cerebral/spinal telangiectases, carotid-carvernous fistulas, ischaemic stroke or TIA, cerebral haemorrhage
Fibromuscular dysplasiaADDoppler ultrasound and angiographyString of beads in affected vascular beds
TIA and ischaemic stroke, cervicocranial dissection, intracerebral aneurysm

Cerebrovascular phenotypes are indicated in italics. AD: autosomal dominant; AR: autosomal recessive.