ISCHEMIC STROKE / ETIOLOGY
Grange syndrome
Created 31/10/2022, last revision 21/04/2023
Etiology
- Grange syndrome results from mutations in the YY1AP1 gene
- homozygous or compound heterozygous mutation in the YY1AP1 gene on chromosome 1q22
- the parents of an individual with an autosomal recessive condition carry one copy of the mutated gene, but typically do not show signs and symptoms
- homozygous or compound heterozygous mutation in the YY1AP1 gene on chromosome 1q22
- the protein produced by this gene is part of a group of proteins that play an important role in smooth muscle cell (SMC) regulation
- mutations lead to the cell cycle arrest with reduced proliferation and differentiation of smooth muscle cells
- it is unclear, however, how these changes lead to the narrowing and blockage of the arteries
- it is also unknown how YY1AP1 gene mutations are related to other features, such as bone abnormalities
Clinical presentation
Diagnostic evaluation
- early-onset vasculopathy with brachy- and syndactyly and bone fragility are typical for this syndrome
- oligosymptomatic forms, such as isolated intracranial stenoses, are diagnostic challenge
Vascular imaging (CTA, MRA, DSA)
- stenoses of the internal carotid arteries and MCAs + collateral vessel formation ⇒ moyamoya-like pattern
- signs of inflammation are absent on black blood sequences
- stenosis of renal, celiac, or coronary arteries (US, CTA, DSA, MRA)
Cardiac monitoring
- check ECG regularly (prolonged QT interval has been reported in Grange syndrome)
- TTE (valvular abnormalities, cardiomyopathy)
Genetic testing
- collect DNA samples to identify pathogenic YY1AP1 variant
Management
- no specific therapy
- antiplatelet therapy if stroke or TIA symptoms occur
- manage vascular risk factors in adults
- consider angioplasty of carotid, renal or celiac stenoses
- consider intracranial revascularization procedures in selected cases (as with moyamoya)
- genetic counseling