Which genetic tests are recommended for confirming a diagnosis of Charcot-Marie-Tooth Disease in primary care?

Genetic testing to confirm a diagnosis of Charcot-Marie-Tooth (CMT) disease in primary care should begin with targeted testing for the most common genetic abnormalities, particularly the PMP22 gene duplication/deletion, which accounts for the majority of CMT type 1 cases. This initial test is recommended because it is the most frequent cause of demyelinating CMT and can be efficiently detected by techniques such as multiplex ligation-dependent probe amplification (MLPA) or microarray analysis NICE CKS.

If PMP22 testing is negative, further genetic testing should be guided by the clinical phenotype and electrophysiological findings, focusing on other common CMT-related genes such as GJB1, MPZ, and MFN2. These genes are associated with different CMT subtypes and can be assessed using next-generation sequencing (NGS) panels designed for hereditary neuropathies, which are increasingly accessible and provide comprehensive coverage Klein 2020Pisciotta & Shy 2023.

Primary care clinicians should consider referral to a specialist or genetic counselling service for interpretation of complex genetic results and to guide further testing if initial targeted tests are inconclusive. This approach aligns with clinical practice guidelines emphasizing a stepwise genetic testing strategy starting with the most common mutations and expanding based on phenotype and family history Sivera Mascaró et al. 2025 NICE CKS.