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 ¹.

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, 2020; Pisciotta and 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) ¹.