Grange syndrome
Grange syndrome is a rare condition characterized by the narrowing or blockage of arteries that supply blood to vital organs, often accompanied by skeletal and heart abnormalities.
Overview
Grange syndrome is a rare condition that primarily affects the blood vessels. It is characterized by narrowing (stenosis) or blockage (occlusion) of arteries that supply blood to various organs and tissues, including the kidneys, brain, and heart. Stenosis or occlusion of the renal arteries can result in chronic high blood pressure (hypertension). Blockage of the cerebral arteries can cause a stroke.
Symptoms
- Short stature
- Brachydactyly (short fingers and toes)
- Syndactyly (fusion of some fingers or toes)
- Fragile bones prone to breakage
- Learning disabilities
- Heart defects present from birth
Causes
Grange syndrome results from mutations in the YY1AP1 gene. The protein produced from this gene is part of a complex that helps regulate critical cellular functions, including gene activity, DNA repair, cell specialization, and cell growth and division. Researchers believe this protein complex plays a particularly important role in smooth muscle cells, which line the blood vessels.
Mutations in the YY1AP1 gene likely disrupt the function of the complex, leading to reduced proliferation and differentiation of smooth muscle cells. It is currently unclear how these changes lead to the narrowing and blockage of arteries or how they relate to bone abnormalities and learning disabilities.
Inheritance
This condition is thought to be inherited in an autosomal recessive pattern, which means both copies of the YY1AP1 gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.