PMP22-Related Neuropathies: A Systematic Review

Area of Science:

• Neurology
• Genetics
• Clinical Medicine

Background:

• PMP22-related neuropathies encompass Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP).
• Rarer phenotypes include CMT1E and Dejerine-Sottas syndrome (DSS), often linked to PMP22 sequence variants.
• These disorders are predominantly demyelinating neuropathies.

Purpose of the Study:

• To systematically review PMP22-related neuropathies reported in recent literature.
• To synthesize clinical, neurophysiological, and genetic data from genetically confirmed cases.
• To identify diagnostic trends and areas for improved reporting.

Main Methods:

• A PRISMA-compliant systematic review of PubMed and Scopus databases (January 2015-August 2025).
• Inclusion of 127 studies with 4493 patients reporting genetically confirmed PMP22-related neuropathies.
• Pooled counts and proportions were synthesized due to heterogeneous data reporting.

Main Results:

• Copy-number variants (duplication/deletion at 17p12) accounted for the majority of cases (95.2%).
• Phenotypes included CMT1A (75.4%), HNPP (20.9%), CMT1E (2.6%), and DSS (1.2%).
• Weakness/foot drop was a common symptom; neurophysiology showed demyelinating patterns, with specific nerve involvement varying by phenotype.

Conclusions:

• PMP22 copy-number variants are the primary cause of these neuropathies.
• Sequence variants are associated with distinct, rarer phenotypes like CMT1E/DSS.
• Standardized reporting of clinical and neurophysiological data is essential for future research and diagnosis.