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Hereditary Neuropathy with Liability to Pressure Palsies

Synonyms: Hereditary Pressure Sensitive Neuropathy, HNPP
, MD
Seattle VA Medical Center
Departments of Neurology and Medicine
University of Washington
Seattle, Washington

Initial Posting: ; Last Update: September 25, 2014.

Summary

Clinical characteristics.

Hereditary neuropathy with liability to pressure palsies (HNPP) is characterized by repeated focal pressure neuropathies such as carpal tunnel syndrome and peroneal palsy with foot drop. The first attack usually occurs in the second or third decade. Recovery from acute neuropathy is often complete; when recovery is not complete, the resulting disability is usually mild. Some affected individuals also have signs of a mild to moderate peripheral neuropathy.

Diagnosis/testing.

The diagnosis of HNPP is established in an adult with recurrent focal compression neuropathies who has a family history consistent with autosomal dominant inheritance. PMP22 is the only gene known to be associated with HNPP. A contiguous gene deletion of chromosome 17p11.2 that includes PMP22 is present in approximately 80% of affected individuals; the remaining 20% have a pathogenic variant in PMP22.

Management.

Treatment of manifestations: A wrist splint may alleviate carpal tunnel syndrome; ankle-foot orthoses (AFOs) may alleviate foot drop.

Prevention of primary manifestations: Protective pads at elbows or knees may prevent pressure and trauma to local nerves.

Agents/circumstances to avoid: Prolonged sitting with legs crossed; prolonged leaning on elbows; occupations requiring repetitive movements of the wrist; rapid weight loss; vincristine.

Other: Surgical decompression of nerves is not beneficial and may cause harm.

Genetic counseling.

HNPP is inherited in an autosomal dominant manner. Each child of an affected individual is at a 50% risk of inheriting the PMP22 pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant has been identified in the family; however, requests for prenatal testing for typically adult-onset conditions such as HNPP are not common.

Diagnosis

Clinical Diagnosis

The diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP) is established in an adult with (1) recurrent focal compression neuropathies and (2) family history consistent with autosomal dominant inheritance.

Findings that support the diagnosis include the following:

  • Mild polyneuropathy, with or without symptoms
  • Evidence on physical examination of previous nerve palsy such as focal weakness, atrophy, or sensory loss
  • Absent ankle reflexes (50%-80%)
  • Diffusely reduced tendon reflexes (15%-30%)
  • Mild to moderate pes cavus foot deformity (20%)

Electrophysiologic studies are usually abnormal:

  • Prolongation of distal nerve conduction latencies (e.g., of the median nerve at the wrist) occurs in essentially all individuals whether symptomatic or asymptomatic.
  • According to Mouton et al [1999], the key electrophysiologic diagnostic features are bilateral slowing of sensory and motor nerve conduction at the carpal tunnel with at least one additional abnormal finding for motor conduction in one peroneal nerve. Infante et al [2001] emphasize the need to evaluate sensory conduction in the sural nerve and motor conduction in at least two nerves across usual entrapment sites, especially the ulnar nerve at the elbow. Li et al [2002] found evidence for prolonged distal motor latencies in the median and peroneal nerves but not ulnar or tibial nerves.
  • Nerve conduction velocity (NCV) may be delayed at the site of compression.
  • General motor NCVs are usually normal (>40 m/s); a few individuals have electrical evidence of a mild diffuse polyneuropathy.

Sural nerve biopsy often shows evidence of demyelination and "tomaculous" (focal, sausage-like enlargement of the nerve) change. Tomaculous change is not specific and has been noted occasionally in other neuropathies.

Molecular Genetic Testing

Gene. PMP22 is the only gene in which mutation is known to cause HNPP.

Table 1.

Molecular Genetic Testing Used in HNPP

Gene 1Test MethodProportion of Probands with a Pathogenic Variant Detectable by This Method
PMP22Deletion/duplication analysis 2~80%
Sequence analysis 3~20%
1.

See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.

2.

Testing that identifies exon or whole-gene deletions/duplications not detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Included in the variety of methods that may be used are: quantitative PCR, long-range PCR, long polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) [Lorentzos et al 2003, Thiel et al 2003], multiplex ligation-dependent probe amplification (MLPA) [Sutton et al 2004], fluorescence in situ hybridization (FISH) [Mohammed & Shaffer 2003] and chromosomal microarray (CMA) that includes this gene/chromosome segment.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Testing Strategy

One genetic testing strategy to confirm/establish the diagnosis in a proband is molecular genetic testing of PMP22 first using deletion/duplication analysis. If the 1.5-Mb deletion including PMP22 is not detected using deletion/duplication analysis, sequence analysis should be performed.

An alternative genetic testing strategy is use of a multigene panel that includes PMP22 and other genes of interest (see Differential Diagnosis). Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.

For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.

Clinical Characteristics

Clinical Description

Hereditary neuropathy with liability to pressure palsies (HNPP) is characterized by recurrent sensory and motor neuropathy in a single nerve beginning in adolescence or young adulthood. The most common presenting symptom of HNPP is the acute onset of a non-painful focal sensory and motor neuropathy in a single nerve (mononeuropathy) [Pareyson et al 1996, Kumar et al 2002, Li et al 2004]. Some individuals experience transient sensory phenomena without weakness. History of actual physical compression of the nerve may or may not be present.

Occasional episodes have been reported during pregnancy, perhaps related to physiologic changes such as soft tissue swelling and edema. The nerve palsies often recur over a period of many years, but some individuals have a single episode and some individuals who have a pathogenic variant are asymptomatic.

The first attack generally occurs in the second or third decade, although the age range extends from two to 70 years (mean age at onset: 37). Radial nerve palsy has been reported in a two-year-old with HNPP [Hardon et al 2002] and peroneal nerve palsies have been reported shortly after birth [Goikhman et al 2003].

Potulska-Chromik et al [2014] describe onset between ages four and 18 years in seven children presenting with mononeuropathies or brachial plexopathy.

Males and females are equally affected.

The following are the most common sites of focal neuropathy (in decreasing order of frequency):

  • The peroneal nerve at the fibular head causing foot drop
  • The ulnar nerve at the elbow, causing hypothenar and interossei muscle weakness and atrophy with sensory loss over the lateral aspect of the hand
  • The median nerve at the wrist causing carpal tunnel syndrome with thenar muscle weakness and atrophy and sensory loss over the thumb and index finger [Del Colle et al 2003]
  • The brachial plexus and radial nerve, causing transient sensory symptoms and hand pain [Marriott et al 2002].

Full recovery over a period of days to months occurs in approximately 50% of episodes. Incomplete recovery is fairly common, but the remaining symptoms are rarely severe. Poor recovery correlates with a history of prolonged focal compression of the nerve [Koike et al 2005].

Symptomatic individuals have the frustration and disability associated with recurrent pressure palsies, although the degree of handicap in performing activities of daily living is usually not severe.

Yilmaz et al [2015] found that 24 (75%) of 32 patients with HNPP had symptoms of pain and pain was the initial symptom in four (12%). Nine subjects (28%) had symptoms suggesting fibromyalgia, which may be a common early clinical diagnosis.

In addition to the typical presentation of HNPP, Mouton et al [1999] described five other phenotypes:

  • Recurrent positional short-term sensory symptoms
  • Progressive mononeuropathy
  • CMT-like polyneuropathy
  • Chronic sensory polyneuropathy
  • Chronic inflammatory demyelinating polyneuropathy-like disorder [Korn-Lubetzki et al 2002]

In 41 (56%) of 73 subjects with HNPP Luigetti et al [2014] found "atypical" presentations that included generalized weakness and cramps, chronic ulnar neuropathy, carpal tunnel syndrome, chronic sensory polyneuropathy, Guillain-Barre-like symptoms, and CMT phenotype.

Note: Some individuals may be asymptomatic.

Other findings reported in a few individuals:

Chanson et al [2013] reported decreased brain white-matter volume in 70% of patients with HNPP or CMT1A (15 individuals in each group). Also, 47% of subjects had mild impairment of memory or executive function on cognitive testing. These findings need replication and confirmation.

Genotype-Phenotype Correlations

Persons with the PMP22 frameshift variant p.Arg95GlyfsTer128 have a typical HNPP phenotype but are also more likely to have an associated clinically evident motor/sensory neuropathy mimicking Charcot-Marie-Tooth neuropathy type 1 (CMT1; see CMT Overview) [Lenssen et al 1998]. A similar phenotype has been described in individuals with other single-nucleotide variants in PMP22 [Bellone et al 2006, Li et al 2007, Muglia et al 2007, Moszyńska et al 2009, Taioli et al 2011] and in a family with a novel frameshift variant [Yurrebaso et al 2014].

Shy et al [2006] described an HNPP phenotype associated with the p.Thr118Met pathogenic variant in PMP22.

Al-Thihli et al [2008] reported a child severely affected with CMT having two pathogenic PMP22 alleles: a PMP22 deletion inherited from the mother and deletion of exons 2 and 3 of PMP22 inherited from the father. Abe et al [2010] reported a child with a severe CMT syndrome who was also compound heterozygous for two different PMP22 deletions.

Penetrance

Many individuals with the PMP22 1.5-Mb deletion have few (or no) symptoms and remain undiagnosed. The penetrance is not known.

Anticipation

Anticipation has not been described.

Nomenclature

Hereditary neuropathy with liability to pressure palsies was previously referred to as tomaculous neuropathy, recurrent pressure-sensitive neuropathy, and "tulip-bulb digger's palsy" or "potato-grubbing palsy" [Koehler 2003]. In 2012 Koehler and Baas documented a PMP22 deletion in the original Dutch family, reported by De Jong in 1947 as having potato-grubbing palsy [Koehler & Baas 2012].

Prevalence

The prevalence of HNPP is unknown; it is estimated at two to five cases per 100,000 population. The actual prevalence may be higher because of under-diagnosis.

Meretoja et al [1997] found the prevalence in Finland to be 16:100,000.

Differential Diagnosis

Pressure palsies are most commonly the result of environmentally acquired physical compression of peripheral nerves. The most common are carpal tunnel syndrome with compression of the median nerve at the wrist, peroneal pressure palsy with compression of the superficial peroneal nerve at the fibular head, and ulnar nerve compression at the elbow. The signs and symptoms of compression neuropathy in hereditary neuropathy with liability to pressure palsies (HNPP) are the same as those of the acquired type. Thus, HNPP is part of the broad differential diagnosis of both compression neuropathies and general peripheral neuropathies, including the hereditary neuropathies and Charcot-Marie-Tooth (CMT) syndrome (see CMT Overview).

Persons with an underlying polyneuropathy, such as those with diabetes mellitus, are at increased risk for compression neuropathies.

HNPP is not a common cause of isolated idiopathic carpal tunnel syndrome [Stockton et al 2001, Sander et al 2005].

The proportion of individuals with a single episode of compression neuropathy who have a 17p11 deletion or PMP22 pathogenic variant is not known. However, because some individuals with HNPP may have no family history of neuropathy, a single episode of nerve compression, or a de novo pathogenic variant, some authors have advocated molecular genetic testing of individuals with a negative family history who have compression neuropathy. A more selective approach is to test only those individuals with one of the following:

  • More than one episode of compression neuropathy
  • One episode of compression neuropathy and an unexplained polyneuropathy
  • One episode of compression neuropathy and a family history of neuropathy

HNPP sometimes involves the brachial plexus, thus overlapping with hereditary neuralgic amyotrophy, a distinct disorder that maps to 17q. Stögbauer et al [2000] contrast the clinical features of HNPP and hereditary neuralgic amyotrophy.

It has been hypothesized that having a genetic neuropathy, such as HNPP, may predispose an individual to developing other immune-mediated neuropathies. For example, Remiche et al [2013] reported a previously undiagnosed woman with HNPP who developed chronic inflammatory demelyinating polyradiculoneuropathy (ClDP) following an influenza AH1N1 vaccination. The diagnosis of HNPP was made after she developed CIDP.

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with hereditary neuropathy with liability to pressure palsies (HNPP), the following evaluations are recommended:

  • History of focal nerve symptoms
  • Family history
  • Neurologic examination
  • Electromyography / nerve conduction velocity (EMG/NCV)
  • Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Transient bracing, such as with a wrist splint or ankle-foot orthosis (AFO), may be useful. Some individuals with residual foot drop may permanently use an AFO.

Prevention of Primary Manifestations

Protective pads at elbows or knees may prevent pressure and trauma to local nerves.

Prevention of Secondary Complications

Bracing of weak muscles, such as ankle-foot-orthosis for foot drop, may prevent injury.

Agents/Circumstances to Avoid

Risk factors for pressure palsies (and thus activities to avoid) include prolonged sitting with legs crossed, occupations requiring repetitive movements of the wrist, prolonged leaning on elbows, and rapid weight loss [Cruz-Martinez et al 2000, Marriott et al 2002].

Vincristine, commonly used in the chemotherapy of lymphoma, has been reported to exacerbate HNPP [Kalfakis et al 2002].

Evaluation of Relatives at Risk

Relatives at risk may wish to clarify their genetic status by undergoing molecular genetic testing; if found to have the PMP22 pathogenic variant identified in an affected family member, they can choose to avoid the aforementioned agents and circumstances.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov in the US and www.ClinicalTrialsRegister.eu in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Other

Controversy exists as to whether surgical decompression of nerves is of benefit. Because spontaneous recovery is common and because no systematic controlled study of surgical intervention has been done, this decision must be made on an individual basis, taking into consideration knowledge of the natural history of the disease. Although Earle and Zochodne [2013] reported two cases of clinical and electrophysiologic improvement after carpal tunnel decompression surgery, there is a developing consensus that surgical repair of carpal tunnel syndrome is of little benefit to individuals with HNPP and that transposition of the ulnar nerve at the elbow may actually produce poor results [Lazar et al 2007].

No specific treatment for the underlying genetic or biochemical defect exists and no special diet or vitamin regimen is known to alter the natural course of HNPP.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Hereditary neuropathy with liability to pressure palsies (HNPP) is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

Sibs of a proband

  • The risk to the sibs of the proband depends on the genetic status of the proband's parents.
  • If a parent is affected, the risk to the sibs is 50%.
  • When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low.
  • The sibs of a proband with clinically unaffected parents are still at increased risk for HNPP because of the possibility of reduced penetrance in a parent.
  • If the PMP22 pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the risk to sibs is low but greater than that of the general population because of the possibility of germline mosaicism.
  • Although no instances of germline mosaicism have been reported, it remains a possibility.

Offspring of a proband. Each child of an individual with HNPP has a 50% chance of inheriting the PMP22 pathogenic variant.

Other family members of a proband

  • The risk to other family members depends on the genetic status of the proband's parents.
  • If a parent is affected, his or her family members are at risk.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and avoidance of certain agents and circumstances.

Testing of at-risk asymptomatic adult relatives of individuals with HNPP is possible after molecular genetic testing has identified the specific pathogenic variant in the family. Such testing should be performed in the context of formal genetic counseling. This testing is not useful in predicting age of onset, severity, type of symptoms, or rate of progression in asymptomatic individuals. Testing of asymptomatic at-risk individuals with nonspecific or equivocal symptoms is predictive testing, not diagnostic testing.

Testing of asymptomatic at-risk individuals younger than age 18 years who are at risk for adult-onset disorders for which no treatment exists is not considered appropriate, primarily because it negates the autonomy of the child with no compelling benefit. Further, concern exists regarding the potential unhealthy adverse effects that such information may have on family dynamics, the risk of discrimination and stigmatization in the future, and the anxiety that such information may cause.

Testing is appropriate to consider in symptomatic individuals in a family with an established diagnosis of HNPP regardless of age.

See also the National Society of Genetic Counselors position statement on genetic testing of minors for adult-onset conditions and the American Academy of Pediatrics and American College of Medical Genetics and Genomics policy statement: ethical and policy issues in genetic testing and screening of children.

Considerations in families with an apparent de novo pathogenic variant. When neither parent of a proband with HNPP has the pathogenic variant or clinical evidence of the disorder, the PMP22 pathogenic variant is likely de novo. However, possible non-medical explanations including alternate paternity or maternity (i.e., with assisted reproduction) or undisclosed adoption could also be explored.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy. Similarly, decisions about testing to determine the genetic status of at-risk asymptomatic family members are best made before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Once the PMP22 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for HNPP are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Hereditary Neuropathy Foundation, Inc.
    432 Park Avenue South
    4th Floor
    New York NY 10016
    Phone: 855-435-7268 (toll-free); 212-722-8396
    Fax: 917-591-2758
    Email: info@hnf-cure.org
  • National Library of Medicine Genetics Home Reference
  • Charcot-Marie-Tooth Association (CMTA)
    PO Box 105
    Glenolden PA 19036
    Phone: 800-606-2682 (toll-free); 610-499-9264
    Fax: 610-499-9267
    Email: info@cmtausa.org
  • European Charcot-Marie-Tooth Consortium
    Department of Molecular Genetics
    University of Antwerp
    Antwerp Antwerpen B-2610
    Belgium
    Fax: 03 2651002
    Email: gisele.smeyers@ua.ac.be

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Hereditary Neuropathy with Liability to Pressure Palsies: Genes and Databases

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Hereditary Neuropathy with Liability to Pressure Palsies (View All in OMIM)

162500NEUROPATHY, HEREDITARY, WITH LIABILITY TO PRESSURE PALSIES; HNPP
601097PERIPHERAL MYELIN PROTEIN 22; PMP22

Gene structure. PMP22 spans approximately 5 kb and has four exons. For a detailed summary of gene and protein information, see Table A, Gene.

Pathogenic variants. The molecular defect present in 80% of affected individuals is a 1.5-Mb deletion at 17p11.2 that includes PMP22. This is the reciprocal of the 1.5-Mb duplication that occurs in Charcot-Marie-Tooth neuropathy type 1A (see CMT Overview). These rearrangements are the result of unequal crossing over following misalignment of flanking repeat sequences at this chromosomal location. HNPP is likely to be the result of a gene dosage effect.

Approximately 20% of families with HNPP have a variety of PMP22 single-nucleotide variants (SNVs) that produce frameshifts, premature termination of translation, or other abnormalities [Young et al 1997, Lenssen et al 1998, Stögbauer et al 2000, van de Wetering et al 2002, Kleopa et al 2004]. The clinical and molecular aspects of other SNVs associated with the HNPP phenotype are reviewed by Stögbauer et al [2000] and van de Wetering et al [2002]. These include pathogenic variants resulting in frameshifts, premature termination translation, a 5' splice site variant, and a variant affecting the junction of the extracellular loop and the first transmembrane domain of PMP22. Additionally, Meuleman et al [2001] have reported a 3' splice site variant, preceding coding exon 3, resulting in a mild HNPP phenotype. The p.Arg95GlyfsTer128 pathogenic variant not only results in a frameshift at residue 95 but also creates a new translation termination site, thereby adding 61 more amino acids to the length of the protein. See Table 2.

Table 2.

Selected PMP22 Pathogenic Variants

DNA Nucleotide ChangePredicted Protein Change
(Alias 1)
Reference Sequences
c.281_282insGp.Arg95GlyfsTer128 2
(Gly94fs)
NM_000304​.2
NP_000295​.1
c.353C>Tp.Thr118Met 2

Note on variant classification: Variants listed in the table have been provided by the author. GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome

Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

1.

Variant designation that does not conform to current naming conventions

2.

Normal gene product. Peripheral myelin protein 22 is a 160-amino acid protein that is present in compact myelin and has four transmembrane domains.

Abnormal gene product. HNPP is associated with decreased mRNA message for PMP22 and decreased peripheral myelin protein 22 in peripheral nerve [Gabriel et al 1997, Schenone et al 1997a, Schenone et al 1997b]. Guo et al [2014] have shown that PMP22 deficiency disrupts myelin junctions resulting in impaired propagation of nerve action potentials.

References

Published Guidelines / Policy Statements

  • Committee on Bioethics, Committee on Genetics, and American College of Medical Genetics and Genomics Social, Ethical, Legal Issues Committee. Ethical and policy issues in genetic testing and screening of children. Available online. 2013. Accessed 6-28-18 [PubMed: 23428972]
  • National Society of Genetic Counselors. Position statement on genetic testing of minors for adult-onset disorders. Available online. 2017. Accessed 6-28-18

Literature Cited

  • Abe A, Nakamura K, Kato M, Numakura C, Honma T, Seiwa C, Shirahata E, Itoh A, Kishikawa Y, Hayasaka K. Compound heterozygous PMP22 deletion mutations causing severe Charcot-Marie-Tooth disease type 1. J Hum Genet. 2010;55:771–3. [PubMed: 20739940]
  • Al-Thihli K, Rudkin T, Carson N, Poulin C, Melançon S, Der Kaloustian VM. Compound heterozygous deletions of PMP22 causing severe Charcot-Marie-Tooth disease of the Dejerine-Sottas disease phenotype. Am J Med Genet A. 2008;146A:2412–6. [PubMed: 18698610]
  • Asahina M, Kuwabara S, Hattori T, Asahina M, Katayama K. Respiratory insufficiency in a patient with hereditary neuropathy with liability to pressure palsy. J Neurol Neurosurg Psychiatry. 2000;68:110–1. [letter] [PMC free article: PMC1760634] [PubMed: 10671122]
  • Bellone E, Balestra P, Ribizzi G, Schenone A, Zocchi G, Di Maria E, Ajmar F, Mandich P. An abnormal mRNA produced by a novel PMP22 splice site mutation associated with HNPP. J Neurol Neurosurg Psychiatry. 2006;77:538–40. [PMC free article: PMC2077485] [PubMed: 16199442]
  • Beydoun SR, Sykes SN, Ganguly G, Lee TS. Hereditary neuropathy with liability to pressure palsies: description of seven patients without known family history. Acta Neurol Scand. 2008;117:266–72. [PubMed: 17922888]
  • Chanson JB, Echaniz-Laguna A, Blanc F, Lacour A, Ballonzoli L, Kremer S, Namer IJ, Lannes B, Tranchant C, Vermersch P, de Seze J. Central nervous system abnormalities in patients with PMP22 gene mutations: a prospective study. J Neurol Neurosurg Psychiatry. 2013;84:392–7. [PubMed: 23243264]
  • Corwin HM, Girardet RE. Hereditary neuropathy with liability to pressure palsies mimicking hypoglossal nerve injuries. Neurology. 2003;61:1457–8. [PubMed: 14638986]
  • Cruz-Martinez A, Arpa J, Palau F. Peroneal neuropathy after weight loss. J Peripher Nerv Syst. 2000;5:101–5. [PubMed: 10905469]
  • Dacković J, Rakocević-Stojanović V, Pavlović S, Zamurović N, Dragasević N, Romac S, Apostolski S. Hereditary neuropathy with liability to pressure palsies associated with central nervous system myelin lesions. Eur J Neurol. 2001;8:689–92. [PubMed: 11784354]
  • Del Colle R, Fabrizi GM, Turazzini M, Cavallaro T, Silvestri M, Rizzuto N. Hereditary neuropathy with liability to pressure palsies: electrophysiological and genetic study of a family with carpal tunnel syndrome as only clinical manifestation. Neurol Sci. 2003;24:57–60. [PubMed: 12827539]
  • Earle N, Zochodne DW. Is carpal tunnel decompression warranted for HNPP? J Peripher Nerv Syst. 2013;18:331–5. [PubMed: 24171697]
  • Gabriel JM, Erne B, Pareyson D, Sghirlanzoni A, Taroni F, Steck AJ. Gene dosage effects in hereditary peripheral neuropathy. Expression of peripheral myelin protein 22 in Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies nerve biopsies. Neurology. 1997;49:1635–40. [PubMed: 9409359]
  • Goikhman I, Meer J, Zelnik N. Hereditary neuropathy with liability to pressure palsies in infancy. Pediatr Neurol. 2003;28:307–9. [PubMed: 12849887]
  • Guo J, Wang L, Zhang Y, Wu J, Arpag S, Hu B, Imhof BA, Tian X, Carter BD, Suter U, Li J. Abnormal junctions and permeability of myelin in PMP22-deficient nerves. Ann Neurol. 2014;75:255–65. [PMC free article: PMC4206215] [PubMed: 24339129]
  • Hardon WJ, van Alfen N, Zwarts MJ, Rotteveel JJ. Hereditary neuropathy with liability to pressure palsies in a toddler. Neurology. 2002;59:2008. [PubMed: 12499508]
  • Horowitz SH, Spollen LE, Yu W. Hereditary neuropathy with liability to pressure palsy: fulminant development with axonal loss during military training. J Neurol Neurosurg Psychiatry. 2004;75:1629–31. [PMC free article: PMC1738805] [PubMed: 15489403]
  • Infante J, Garcia A, Combarros O, Mateo JI, Berciano J, Sedano MJ, Gutierrez-Rivas EJ, Palau F. Diagnostic strategy for familial and sporadic cases of neuropathy associated with 17p11.2 deletion. Muscle Nerve. 2001;24:1149–55. [PubMed: 11494267]
  • Kalfakis N, Panas M, Karadima G, Floroskufi P, Kokolakis N, Vassilopoulos D. Hereditary neuropathy with liability to pressure palsies emerging during vincristine treatment. Neurology. 2002;59:1470–1. [PubMed: 12427913]
  • Kleopa KA, Georgiou DM, Nicolaou P, Koutsou P, Papathanasiou E, Kyriakides T, Christodoulou K. A novel PMP22 mutation Ser22Phe in a family with hereditary neuropathy with liability to pressure palsies and CMT1A phenotypes. Neurogenetics. 2004;5:171–5. [PubMed: 15205993]
  • Koehler PJ. Hereditary neuropathy with liability to pressure palsies: the first publication (1947). Neurology. 2003;60:1211–3. [PubMed: 12682341]
  • Koehler PJ, Baas F. Hereditary neuropathy with liability to pressure palsies. Diagnosis in the first family (1947) confirmed. J Peripher Nerv Syst. 2012;17:412–3. [PubMed: 23279343]
  • Koike H, Hirayama M, Yamamoto M, Ito H, Hattori N, Umehara F, Arimura K, Ikeda S, Ando Y, Nakazato M, Kaji R, Hayasaka K, Nakagawa M, Sakoda S, Matsumura K, Onodera O, Baba M, Yasuda H, Saito T, Kira J, Nakashima K, Oka N, Sobue G. Age associated axonal features in HNPP with 17p11.2 deletion in Japan. J Neurol Neurosurg Psychiatry. 2005;76:1109–14. [PMC free article: PMC1739771] [PubMed: 16024889]
  • Korn-Lubetzki I, Argov Z, Raas-Rothschild A, Wirguin I, Steiner I. Family with inflammatory demyelinating polyneuropathy and the HNPP 17p12 deletion. Am J Med Genet. 2002;113:275–8. [PubMed: 12439896]
  • Kumar N, Muley S, Pakiam A, Parry GJ. Phenotypic Variability Leads to Under-recognition of HNPP. J Clin Neuromuscul Dis. 2002;3:106–12. [PubMed: 19078663]
  • Lazar CC, Auquit-Auckbur I, Milliez PY. Hereditary neuropathy with liability to pressure palsies (HNPP) in hand surgery: reminds and warn against a usually unrecognised disease. Ann Chir Plast Esthet. 2007;52:606–8. [PubMed: 17030391]
  • Lenssen PP, Gabreels-Festen AA, Valentijn LJ, Jongen PJ, van Beersum SE, van Engelen BG, van Wensen PJ, Bolhuis PA, Gabreels FJ, Mariman EC. Hereditary neuropathy with liability to pressure palsies. Phenotypic differences between patients with the common deletion and a PMP22 frame shift mutation. Brain. 1998;121:1451–8. [PubMed: 9712007]
  • Li J, Ghandour K, Radovanovic D, Shy RR, Krajewski KM, Shy ME, Nicholson GA. Stoichiometric alteration of PMP22 protein determines the phenotype of hereditary neuropathy with liability to pressure palsies. Arch Neurol. 2007;64:974–8. [PubMed: 17620487]
  • Li J, Krajewski K, Lewis RA, Shy ME. Loss-of-function phenotype of hereditary neuropathy with liability to pressure palsies. Muscle Nerve. 2004;29:205–10. [PubMed: 14755484]
  • Li J, Krajewski K, Shy ME, Lewis RA. Hereditary neuropathy with liability to pressure palsy: the electrophysiology fits the name. Neurology. 2002;58:1769–73. [PubMed: 12084875]
  • Lorentzos P, Kaiser T, Kennerson ML, Nicholson GA. A rapid and definitive test for Charcot-Marie-Tooth 1A and hereditary neuropathy with liability to pressure palsies using multiplexed real-time PCR. Genet Test. 2003;7:135–8. [PubMed: 12885335]
  • Luigetti M, Del Grande A, Conte A, Lo Monaco M, Bisogni G, Romano A, Zollino M, Rossini PM, Sabatelli M. Clinical, neurophysiological and pathological findings of HNPP patients with 17p12 deletion: a single-centre experience. J Neurol Sci. 2014;341:46–50. [PubMed: 24726093]
  • Mäkelä JP, Ramstad R, Mattila V, Pihlajamäki H. Brachial plexus lesions after backpack carriage in young adults. Clin Orthop Relat Res. 2006;(452):205–9. [PubMed: 16906084]
  • Marriott M, Macdonell R, McCrory P. Flail arms in a parachutist: an unusual presentation of hereditary neuropathy with liability to pressure palsies. Br J Sports Med. 2002;36:465–6. [PMC free article: PMC1724562] [PubMed: 12453844]
  • Meretoja P, Silander K, Kalimo H, Aula P, Meretoja A, Savontaus ML. Epidemiology of hereditary neuropathy with liability to pressure palsies (HNPP) in south western Finland. Neuromuscul Disord. 1997;7:529–32. [PubMed: 9447611]
  • Meuleman J, Pou-Serradell A, Lofgren A, Ceuterick C, Martin JJ, Timmerman V, Van Broeckhoven C, De Jonghe P. A novel 3'-splice site mutation in peripheral myelin protein 22 causing hereditary neuropathy with liability to pressure palsies. Neuromuscul Disord. 2001;11:400–3. [PubMed: 11369192]
  • Mohammed MS, Shaffer LG. Fluorescence in situ hybridization (FISH) for identifying the genomic rearrangements associated with three myelinopathies. Charcot-Marie-Tooth disease, hereditary neuropathy with liability to pressure palsies, and Pelizaeus-Merzbacher disease. Methods Mol Biol. 2003;217:219–38. [PubMed: 12491936]
  • Moszyńska I, Kabzińska D, Sinkiewicz-Darol E, Kochański A. A newly identified Thr99fsX110 mutation in the PMP22 gene associated with an atypical phenotype of the hereditary neuropathy with liability to pressure palsies. Acta Biochim Pol. 2009;56:627–30. [PubMed: 19830275]
  • Mouton P, Tardieu S, Gouider R, Birouk N, Maisonobe T, Dubourg O, Brice A, LeGuern E, Bouche P. Spectrum of clinical and electrophysiologic features in HNPP patients with the 17p11.2 deletion. Neurology. 1999;52:1440–6. [PubMed: 10227632]
  • Muglia M, Patitucci A, Rizzi R, Ungaro C, Conforti FL, Gabriele AL, Magariello A, Mazzei R, Motti L, Sabadini R, Sprovieri T, Marcello N, Quattrone A. A novel point mutation in PMP22 gene in an Italian family with hereditary neuropathy with liability to pressure palsies. J Neurol Sci. 2007;263:194–7. [PubMed: 17707409]
  • Pareyson D, Scaioli V, Taroni F, Botti S, Lorenzetti D, Solari A, Ciano C, Sghirlanzoni A. Phenotypic heterogeneity in hereditary neuropathy with liability to pressure palsies associated with chromosome 17p11.2-12 deletion. Neurology. 1996;46:1133–7. [PubMed: 8780105]
  • Potulska-Chromik A, Sinkiewicz-Darol E, Ryniewicz B, Lipowska M, Kabzińska D, Kochański A, Kostera-Pruszczyk A. Clinical, electrophysiological and molecular findings in early onset hereditary neuropathy with liability to pressure palsy. Muscle Nerve. 2014;50:914–8. [PubMed: 24668782]
  • Remiche G, Abramowicz M, Mavroudakis N. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated to hereditary neuropathy with liability to pressure palsies (HNPP) and revealed after influenza AH1N1 vaccination. Acta Neurol Belg. 2013;113:519–22. [PubMed: 24146347]
  • Sanahuja J, Franco E, Rojas-Garcia R, Gallardo E, Combarros O, Begue R, Granes P, Illa I. Central nervous system involvement in hereditary neuropathy with liability to pressure palsies: description of a large family with this association. Arch Neurol. 2005;62:1911–4. [PubMed: 16344349]
  • Sander MD, Abbasi D, Ferguson AL, Steyers CM, Wang K, Morcuende JA. The prevalence of hereditary neuropathy with liability to pressure palsies in patients with multiple surgically treated entrapment neuropathies. J Hand Surg Am. 2005;30:1236–41. [PubMed: 16344182]
  • Schenone A, Nobbio L, Caponnetto C, Abbruzzese M, Mandich P, Bellone E, Ajmar F, Gherardi G, Windebank AJ, Mancardi G. Correlation between PMP-22 messenger RNA expression and phenotype in hereditary neuropathy with liability to pressure palsies. Ann Neurol. 1997a;42:866–72. [PubMed: 9403478]
  • Schenone A, Nobbio L, Mandich P, Bellone E, Abbruzzese M, Aymar F, Mancardi GL, Windebank AJ. Underexpression of messenger RNA for peripheral myelin protein 22 in hereditary neuropathy with liability to pressure palsies. Neurology. 1997b;48:445–9. [PubMed: 9040736]
  • Shy ME, Scavina MT, Clark A, Krajewski KM, Li J, Kamholz J, Kolodny E, Szigeti K, Fischer RA, Saifi GM, Scherer SS, Lupski JR. T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy. Ann Neurol. 2006;59:358–64. [PubMed: 16437560]
  • Stockton DW, Meade RA, Netscher DT, Epstein MJ, Shenaq SM, Shaffer LG, Lupski JR. Hereditary neuropathy with liability to pressure palsies is not a major cause of idiopathic carpal tunnel syndrome. Arch Neurol. 2001;58:1635–7. [PubMed: 11594922]
  • Stögbauer F, Young P, Kuhlenbäumer G, De Jonghe P, Timmerman V. Hereditary recurrent focal neuropathies: clinical and molecular features. Neurology. 2000;54:546–51. [PubMed: 10680781]
  • Sutton IJ, Mocroft AP, Lindley VH, Barber RM, Bryon RJ, Winer JB, MacDonald F. Application of multiplex ligation-dependent probe analysis to define a small deletion encompassing PMP22 exons 4 and 5 in hereditary neuropathy with liability to pressure palsies. Neuromuscul Disord. 2004;14:804–9. [PubMed: 15564036]
  • Tackenberg B, Moller JC, Rindock H, Bien S, Sommer N, Oertel WH, Rosenow F, Schepelmann K, Hamer HM, Bandmann O. CNS involvement in hereditary neuropathy with pressure palsies (HNPP). Neurology. 2006;67:2250–2. [PubMed: 17190957]
  • Taioli F, Cabrini I, Cavallaro T, Acler M, Fabrizi GM. Inherited demyelinating neuropathies with micromutations of peripheral myelin protein 22 gene. Brain. 2011;134:608–17. [PubMed: 21252112]
  • Thiel CT, Kraus C, Rauch A, Ekici AB, Rautenstrauss B, Reis A. A new quantitative PCR multiplex assay for rapid analysis of chromosome 17p11.2-12 duplications and deletions leading to HMSN/HNPP. Eur J Hum Genet. 2003;11:170–8. [PubMed: 12634865]
  • van de Wetering RA, Gabreels-Festen AA, Timmerman V, Padberg GM, Gabreels FJ, Mariman EC. Hereditary neuropathy with liability to pressure palsies with a small deletion interrupting the PMP22 gene. Neuromuscul Disord. 2002;12:651–5. [PubMed: 12207933]
  • Verma A. Neuropathic scapuloperoneal syndrome (Davidenkow's syndrome) with chromosome 17p11.2 deletion. Muscle Nerve. 2005;32:668–71. [PubMed: 16007675]
  • Winter WC, Juel VC. Hypoglossal neuropathy in hereditary neuropathy with liability to pressure palsy. Neurology. 2003;61:1154–5. [PubMed: 14581692]
  • Yilmaz U, Bird TT, Carter GT, Wang LH, Weiss MD. Pain in hereditary neuropathy with liability to pressure palsy: an association with fibromyalgia syndrome? Muscle Nerve. 2015 Mar;51(3):385–90. [PubMed: 25042093]
  • Young P, Wiebusch H, Stogbauer F, Ringelstein B, Assmann G, Funke H. A novel frameshift mutation in PMP22 accounts for hereditary neuropathy with liability to pressure palsies. Neurology. 1997;48:450–2. [PubMed: 9040737]
  • Yurrebaso I, Casado OL, Barcena J, Perez de Nanclares G, Aguirre U. Clinical, electrophysiological and magnetic resonance findings in a family with hereditary neuropathy with liability to pressure palsies caused by a novel PMP22 mutation. Neuromuscul Disord. 2014;24:56–62. [PubMed: 24239057]

Suggested Reading

  • Chance PF. Inherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy. Neuromolecular Med. 2006;8:159–74. [PubMed: 16775374]
  • Lupski JR, Garcia CA. Charcot-Marie-Tooth peripheral neuropathies and related disorders. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G, eds. The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID). Chap 227. McGraw-Hill.

Chapter Notes

Revision History

  • 25 September 2014 (me) Comprehensive update posted live
  • 11 May 2010 (me) Comprehensive update posted live
  • 14 January 2008 (me) Comprehensive update posted live
  • 28 September 2005 (me) Comprehensive update posted live
  • 27 August 2003 (me) Comprehensive update posted live
  • 7 April 2003 (tb) Author revisions
  • 20 June 2001 (me) Comprehensive update posted live
  • 28 September 1998 (tb) Review posted live
  • 6 January 1998 (tb) Original submission
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