Grange syndrome

Grange syndrome (also known as Grange occlusive arterial syndrome or stenoses of renal arteries, moyamoya, and congenital heart defects) is an extremely rare autosomal recessive multisystem disorder caused by biallelic pathogenic variants in the YY1AP1 gene (OMIM #602531). The condition is characterized by a distinctive combination of stenosis or occlusion of multiple arteries (including renal, cerebral, and abdominal vessels), congenital heart defects, brachydactyly (short fingers), syndactyly (fused fingers or toes), bone fragility, and learning disabilities or intellectual disability. The arterial involvement can lead to severe renovascular hypertension, moyamoya-like cerebrovascular disease with risk of stroke, and other ischemic complications. The vascular manifestations are among the most clinically significant features and may present in childhood with hypertension that is often difficult to control. Additional features can include short stature, pectus deformities, and other skeletal anomalies. The arterial stenoses are progressive and can affect multiple vascular beds simultaneously, distinguishing this condition from other forms of childhood vasculopathy such as fibromuscular dysplasia. There is currently no cure for Grange syndrome. Treatment is supportive and symptom-directed, focusing on management of hypertension (often requiring multiple antihypertensive medications), surveillance for cerebrovascular complications, cardiac monitoring and intervention for congenital heart defects, and orthopedic management of skeletal abnormalities. Vascular interventions such as angioplasty or surgical revascularization may be considered for critical arterial stenoses, though outcomes can be variable due to the progressive nature of the vasculopathy. Multidisciplinary care involving cardiology, nephrology, neurology, and genetics is essential.

Common questions about Grange syndrome