Moyamoya Disease genetic testing in adults
Moyamoya disease is a rare, progressive cerebrovascular disorder characterized by the narrowing or constriction of the internal carotid arteries and their main branches at the base of the brain. This narrowing causes the development of abnormal collateral vessels that resemble a “puff of smoke” on angiograms—a translation of the Japanese term “moyamoya.” While it is often diagnosed in children, adults can also develop moyamoya disease, sometimes with different clinical presentations and challenges. Recognizing the genetic component of this disease has become increasingly important, particularly in adults, to inform diagnosis, management, and family counseling.
Recent advances suggest that genetics play a significant role in moyamoya disease, although the exact mechanisms are still under investigation. Several gene mutations have been associated with increased susceptibility, with the RNF213 gene being most prominent. Variants of RNF213, especially the p.R4810K mutation, have been identified predominantly in East Asian populations and are considered a major genetic risk factor. However, these genetic markers are not exclusive to specific ethnic groups, and their presence does not necessarily predict disease onset, indicating a complex interplay between genetics and environmental factors.
Genetic testing in adults with moyamoya disease serves multiple purposes. Primarily, it helps confirm the diagnosis, especially in cases where clinical and radiological findings are ambiguous. It also provides valuable information about the risk of disease progression and potential familial occurrence. Since moyamoya can be inherited in an autosomal dominant pattern with incomplete penetrance, identifying a genetic mutation can prompt screening of family members, opening avenues for early intervention and monitoring.
The process of genetic testing involves analyzing blood or saliva samples to detect known mutations associated with moyamoya. Techniques such as next-generation sequencing (NGS) panels targeting relevant genes, including RNF213, are commonly used. These tests can sometimes reveal novel mutations or variants of uncertain significance, which require careful interpretation by genetic counselors and clinicians.
It is important to recognize that genetic testing is not a standalone diagnostic tool. Moyamoya diagnosis primarily relies on neuroimaging studies such as magnetic resonance angiography (MRA) or digital subtraction angiography (DSA), which visualize the characteristic vessel narrowing and collateral formation. Genetic testing complements these imaging techniques by providing insight into underlying susceptibilities and assisting in familial risk assessments.
For adults diagnosed with moyamoya, genetic testing can influence treatment strategies and long-term management. While surgical revascularization remains the mainstay to prevent strokes, understanding genetic predispositions may refine surveillance plans for patients and at-risk relatives. Moreover, identifying genetic factors can contribute to ongoing research efforts aimed at understanding disease mechanisms and developing targeted therapies.
In conclusion, genetic testing in adults with moyamoya disease offers a valuable dimension to diagnosis and management. As research advances, integrating genetic insights with clinical and radiological data holds promise for more personalized, effective care and improved outcomes for patients and their families.
