ISCHEMIC STROKE / CLASSIFICATION AND ETIOPATHOGENESIS

Marfan syndrome

Created 09/05/2023, last revision 09/05/2023

Marfan syndrome is an inherited connective tissue disorder
people with Marfan syndrome are usually tall and thin with unusually long arms, legs, fingers, and toes; the condition may become life-threatening due to aortic involvement

Etiopathogenesis

inherited connective tissue disease
- familial form (75%)
- sporadic form (25%)
AD inheritance, many mutations
- FBN1 gene (15q15-q21.1) and FBN2 gene (5q23-q31) – encodes fibrillin
- TGFBR2 (transforming growth factor-beta receptor 2) gene, locus 3p22
- TGFBR1 gene, locus 9q22
skeletal, ocular, and cardiac involvement typically predominates; vascular involvement is characterized by altered tunica media

Mutations in the FBN1 gene cause connective tissue to be weaker. It is also believed that mutated fibrillin does not control the excess TGFB, and its increased activity leads to pathological changes in various body organs. This regulatory role is also impaired in the case of mutations in the transforming growth factor beta receptor genes, TGFBR1 and TGFBR2.

Clinical presentation

Neurovascular symptoms

stroke due to:
- dissection of cerebral arteries
- cardioembolism (valvular dysfunction, arrhythmias)
- (pseudo) aneurysm formation (rupture or embolization from the sac)

Cardiovascular symptoms

common cause of fatal complications (cause of death in up to 90%)
dilation (up to 80%) or dissection of the ascending aorta [Hwa, 1993]
- incipient dilatation is often seen by the end of the first decade of life
frequent aortic regurgitation, mitral valve prolapse
dilation of the pulmonary artery

Skeletal malformations

tall figure
long, thin limbs
hypermobile joints
- thumb sign – thumb extends beyond the ulnar edge of the hand when fingers are clenched into a fist
- wrist sign – thumb extends beyond index finger when the wrist is grasped
scapula alata
pectus carinatum or excavatum
pes planus
arachnodactyly
scoliosis and other spinal deformities
dolichocephaly

Ophthalmologic symptoms

lens ectopia (up to 50% of cases)
myopia
tendency to retinal detachment

Diagnostic evaluation

typical clinical presentation (may be variable)
vascular imaging (TEE, CTA, MRA) – dilation of the aortic root and ascending and descending aorta
genetic testing
exclude:
- homocystinuria (mental retardation is common)
- Ehlers-Danlos syndrome
- Shprintzen Goldberg syndrome
- Loeys-Dietz syndrome

Diagnostic criteria for Marfan syndrome

Negative family history

aortic root Z-score ≥ 2 / dissection + lens ectopia
aortic root Z-score ≥ 2 / dissection + pozitivní FBN1 mutation
aortic root Z-score ≥ 2 points + systemic score ≥ 7 points
lens ectopia + positive FNB1 regardless of aortic findings

Positive family history

lens ectopia
systemic score ≥ 7 points
aortic root Z-score
- ≥ 2 in those over 20 years of age
- ≥ 3 for under 20 years

Aortic root dilalation in Marfan syndrome

Dilated descending and abdominal aorta in Marfan syndrome

Management

only symptomatic therapy
skeletal monitoring
heart and aorta ultrasound each year
regular ophthalmologic exams
pregnancy is not recommended
standard stroke treatment and prevention