Which test is the preferred initial diagnostic approach for Neurofibromatosis 2?

The preferred initial diagnostic approach for Neurofibromatosis 2 is sequencing followed by deletion/duplication analysis. Neurofibromatosis type 2 (NF2) is primarily caused by mutations in the NF2 gene, which encodes the protein merlin. Genetic testing that includes sequencing the NF2 gene allows for the identification of point mutations. Following sequencing, deletion/duplication analysis is essential to detect any larger genomic alterations, such as deletions or duplications, that may not be captured through standard sequencing methods.

This comprehensive approach ensures that both small and large changes in the NF2 gene are identified, providing a definitive diagnosis. It is particularly important in genetic conditions like NF2 where both types of alterations can significantly contribute to the disease phenotype. While imaging studies may be helpful for evaluating symptoms related to tumor development associated with NF2, they do not provide a genetic diagnosis and are not the primary method recommended for initial diagnosis. Similarly, MLPA (Multiplex Ligation-dependent Probe Amplification) for methylation would be a follow-up tool rather than a first-line approach, and phenotypic assessment alone may miss the molecular underpinnings of the condition. Thus, starting with genetic sequencing followed by deletion/duplication analysis maximizes