Hereditary neuropathy with liability to pressure palsies (HNPP)
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A 25-year-old has recurrent episodes of numbness and weakness after minor nerve compression (e.g., crossing legs, leaning on elbow). Symptoms resolve over weeks.
AD; PMP22 deletion (reciprocal of CMT1A duplication)
- Recurrent focal neuropathies triggered by pressure/trauma
- Episodes typically resolve
- May develop mild background neuropathy over time
- Clinical suspicion from recurrent painless pressure palsies at common compression sites
- Nerve conduction studies show a background demyelinating sensorimotor neuropathy with focal conduction slowing at entrapment sites; sural biopsy (if done) shows tomaculous ("sausage-like") myelin
- Confirm with molecular testing for the recurrent 1.5 Mb 17p12 deletion spanning PMP22 (the reciprocal of the CMT1A duplication); if absent, sequence PMP22 for an intragenic loss-of-function variant
- Preventive counseling: avoid prolonged limb compression, repetitive trauma, and rapid weight loss; use ergonomic padding and positioning
- Supportive care: physical/occupational therapy, splints or braces for foot drop, and pain management; most episodes recover spontaneously
- Caution with positioning during surgery and anesthesia; consider the diagnosis before nerve decompression surgery
"HNPP is the reciprocal of CMT1A": CMT1A = PMP22 duplication (too much myelin protein), HNPP = PMP22 deletion (too little myelin protein). Same gene region on 17p12, opposite dosage effects. Notably, this is opposite the typical paradigm where deletions are more severe than duplications: here the deletion (HNPP) is the milder condition and the duplication (CMT1A) is more severe.