Hereditary Neuropathy with liability to Pressure Palsies
| Hereditary Neuropathy with liability to Pressure Palsies | |
|---|---|
| Synonym | Tomaculous neuropathy, Polyneuropathy familial recurrent |
| Causes | deletion of a 1.5 Mb region on chromosome 17p11.2, which includes the PMP22 gene |
| Inheritance | Autosomal dominant with a de novo mutation rate of approximately 20%. |
| Genetics | heterozygous deletion of PMP22, leading to reduced gene dosage and impaired myelin maintenance. |
| Pathophysiology | Reduced PMP22 protein levels result in myelin instability, making nerves susceptible to pressure-induced conduction block and damage. |
| Classification | HNPP is classified under hereditary demyelinating neuropathies and distinct from other polyneuropathies due to its episodic nature. |
| Risk Factors | Prolonged pressure on nerves, repetitive movements, trauma, rapid weight loss, and certain medications (e.g., vincristine) can exacerbate symptoms. |
| Clinical Features | Recurrent, transient motor and sensory deficits affecting single nerves, commonly in the peroneal and ulnar nerves, leading to weakness, numbness, and atrophy. High rates of chronic neuropathic pain, including widespread pain. |
| Diagnosis | Based on clinical history, electrophysiological studies, and genetic testing confirming PMP22 deletion. |
| DDX | Includes acquired entrapment neuropathies, Charcot-Marie-Tooth disease, chronic inflammatory demyelinating polyneuropathy, and hereditary neuralgic amyotrophy. |
Hereditary Neuropathy with liability to Pressure Palsies (HNPP) is an autosomal dominant disorder of myelination caused by genetic deletion of PMP22. This should not be confused with PMP22 duplication which is see in Charcot-Marie-Tooth disease type 1A. PMP22 expresses is a peripheral myelin protein. The musculoskeletal physician should be aware of the condition as it is commonly associated with neuropathic pain.
Clinical Features
History
The traditional cardinal feature is recurrent acute onset sensory and motor mononeuropathies. These are typically preceded by prolonged pressure or trauma to the peripheral nerve. Common symptoms include foot drop (peroneal nerve), carpal tunnel syndrome (median nerve), sensory loss lateral hand (ulna nerve at elbow), wrist drop (radial nerve), etc. Incomplete recovery is common (50% achieve full recovery of episodes).[1]
The age of onset is typically in the second or third decade. But can occur earlier or later. There is a wide spectrum of severity including asymptomatic individuals. At the severe end the phenotype can mimic CMT.[1]
Traditionally HNPP has been thought of as a "pain-free" neuropathy, however this has been shown to be manifestly incorrect. In fact, neuropathic pain is reported in a high proportion of patients with HNPP across multiple observational studies.
- A report on 19 patients, 8 had neuropathic pain (42%). 7 of these patients had neuropathic foot pain described as "burning, aching, shooting."[2]
- A report on four HNPP patients with neuropathic pain, all with diffuse pain. Three of these four patients met the criteria for fibromyalgia. [3]
- A report on 43 patients identified that 32 of them (74%) had persistent pain. Of the 32 with pain, 24 (55% of the total) were felt to have neuropathic pain, and 27 (62% of total) were felt to have central sensitisation.[4]
- A report on 32 patients found that 24 (75%) had pain, with 10 (31%) having neuropathic pain, and 9 (28%) having fibromyalgia.[5]
A family history is common, but there is a 20% de novo mutation rate.[1]
Examination
Muscle weakness, atrophy, sensory signs, reduced or absent tendon reflexes (most commonly the ankles). Pes cavus is common.[1]
Investigations
EMG and NCS is the first step which show diffuse prolonged conduction latencies in sensory and distal motor nerves plus conduction blocks at entrapment sites. Abnormalities are seen even in asymptomatic patients.
Ultrasound can show increased cross section of nerves at entrapment sites.
Nerve biopsy shows segmental de- and remyelination of varying large fibre loss.[1]
Genetic testing is done to confirm the diagnosis.
Treatment
No specific treatment exists. Management of a pressure palsy attack can include transient bracing. In incomplete recovery (such as foot drop) the bracing may need to be long term.
References
- ā 1.0 1.1 1.2 1.3 1.4 Paassen, Barbara W. van; Kooi, Anneke J. van der; Spaendonck-Zwarts, Karin Y. van; Verhamme, Camiel; Baas, Frank; Visser, Marianne de (2014 Mar 19). "PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies". Orphanet Journal of Rare Diseases (in English). 9: 38. doi:10.1186/1750-1172-9-38. PMID 24646194. Check date values in:
|date=(help) - ā Dukefoss, Tore Thomas; Kleggetveit, Inge Petter; HelĆ„s, Tormod; JĆørum, Ellen (2019-12-18). "Pain and small-fiber affection in hereditary neuropathy with liability to pressure palsies (HNPP)". Scandinavian Journal of Pain (in English). 20 (1): 61ā68. doi:10.1515/sjpain-2019-0090. ISSN 1877-8879.
- ā M Weiss & D Thyerlei. Pain as a Presentation of Hereditary Neuropathy with Liability to Pressure Palsy. Neurology. April 23, 2012. https://www.neurology.org/doi/10.1212/WNL.78.1_supplement.P03.211
- ā Beales, Darren; Fary, Robyn; Little, Cameron; Nambiar, Shruti; Sveinall, Hakon; Yee, Yen Leng; Tampin, Brigitte; Mitchell, Tim (2017-12). "Characterisation of pain in people with hereditary neuropathy with liability to pressure palsy". Journal of Neurology (in English). 264 (12): 2464ā2471. doi:10.1007/s00415-017-8648-z. ISSN 0340-5354. Check date values in:
|date=(help) - ā Yilmaz, Ugur; Bird, Thomas T.; Carter, Gregory T.; Wang, Leo H.; Weiss, Michael D. (2015-02-10). "Pain in hereditary neuropathy with liability to pressure palsy: An association with fibromyalgia syndrome?". Muscle & Nerve. 51 (3): 385ā390. doi:10.1002/mus.24331. ISSN 0148-639X.
Literature Review
Literature Review
- Reviews from the last 7 years: review articles, free review articles, systematic reviews, meta-analyses, NCBI Bookshelf
- Articles from all years: PubMed search, Google Scholar search.
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