Delayed Genetic Diagnosis of a Rare Presentation of Overlapping Peripheral Myelin Protein 22 (PMP22) Neuropathies

Peripheral Myelin Protein 22 (PMP22) is a small integral membrane glycoprotein that is essential for the formation and maintenance of myelin architecture in the peripheral nervous system. Variations of the PMP22 gene can result in a variety of genetic conditions, with some of the most notable being Charcot-Marie-Tooth disease (CMT) as well as Hereditary Neuropathy with Liability to Pressure Palsies (HNPP). The patient had a strong family history of CMT, and she began experiencing recurrent foot drop, sensory loss, extremity weakness, and frequent falls; however, initial genetic testing did not reveal any mutation in the PMP22 gene. This case features the diagnostic challenges associated with inherited neuropathies when clinical suspicion is high but genetic results are initially inconclusive. It also emphasizes the importance of repeat or expanded genetic testing to ensure a timely diagnosis with appropriate management and family genetic counseling.