To assess the utility of a four gene panel for molecular diagnosis of Charcot-Marie-Tooth (CMT) neuropathy.

CMT and related hereditary forms of peripheral neuropathies (PNs) represent a genetically heterogeneous group of disorders with an estimated prevalence of 1 in 2500. However, there are a few genes (PMP22, GJB1, MPZ, and MFN2) with relatively high diagnostic yields, particularly for CMT type 1. As genetic testing moves toward large panels and exome/genome sequencing, the utility of small, targeted panels may be undervalued.

Our data demonstrate that genetic testing for CMT via a thoughtfully designed, small genetic testing panel with well-established genes can be an advantageous option for physicians interested in a test with a high diagnostic yield and low VUS rate. This will reduce the burden for practices with limited genetic counselor resources. If desired, a tiered testing approach with reflex to a larger multi-gene panel or exome sequencing could be considered.