Skip to main content

Advertisement

SpringerLink
Log in

Yield of the PMP22 deletion analysis in patients with compression neuropathies

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Introduction

Hereditary neuropathy with liability to pressure palsies (HNPP) is a rare neuromuscular disorder, mostly caused by PMP22 deletion.

Aim

To determine a yield of the genetic analysis of PMP22 gene deletion in patients with compression neuropathies.

Method

We included 112 patients with clinical suspicion of HNPP diagnosis. Nerve conduction studies (NCS) were performed for motor and sensory nerves bilaterally. Number of the PMP22 gene copies was determined using a real-time polymerase chain reaction (RT-PCR).

Results

PMP22 deletion was found in 34 (30.3%) patients. Patients with genetically confirmed HNPP had 12 years earlier disease onset compared to other patients with compression neuropathies (p < 0.01), more nerves affected during lifespan (5.5 ± 3.5 vs. 3.0 ± 2.0, p < 0.01) and at the time of referral (2.7 ± 2.5 vs. 2.0 ± 1.9, p < 0.05). HNPP patients had positive family history more frequently (p < 0.01). Foot deformities (pes cavus and hammertoe), symmetric muscle atrophy in lower legs and absent muscle reflexes in lower limbs were more common in HNPP patients. NCS abnormalities were also more common in HNPP group. Multiple linear regression analysis identified positive family history (β =  + 0.35, p < 0.01) and decreased sensory conduction velocity in at least three sensory nerves (β =  + 0.40, p < 0.01) as independent predictors of the PMP22 deletion.

Conclusion

Among patients with compression neuropathies, those with a positive family history, earlier symptom onset and NCS abnormalities had a higher chance to have PMP22 deletion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Availability of data and material

Raw data were generated at Neurology Clinic, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Derived data supporting the findings of this study are available from the corresponding author on request.

References

  1. Mouton P, Tardieu S, Gouider R, Birouk N, Maisonobe T, Dubourg O et al (1999) Spectrum of clinical and electrophysiologic features in HNPP patients with the 17p11.2 deletion. Neurology 52:1440–1446

    Article  CAS  Google Scholar 

  2. Foley C, Schofield I, Eglon G, Bailey G, Chinnery PF, Horvath R (2012) Charcot Marie-Tooth disease in Northern England. J Neurol Neurosurg Psychiatry 83:572–573

    Article  Google Scholar 

  3. van Paassen BW, van der Kooi AJ, van Spaendonck-Zwarts KY, Verhamme C, Baas F, de Visser M (2014) PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies. Orph J Rare Dis 9:38

    Article  Google Scholar 

  4. Bird TD (1998) Hereditary neuropathy with liability to pressure palsies. Gene Rev 32:1993–2020

    Google Scholar 

  5. Nelis E, Van Broeckhoven C, De Jonghe P, Löfgren A, Vandenberghe A, Latour P et al (1996) Estimation of the mutation frequencies in Charcot-Marietooth disease type 1 and hereditary neuropathy with liability to pressure palsies: a European collaborative study. Eur J Hum Genet 4:25–33

    Article  CAS  Google Scholar 

  6. Pareyson D, Scaioli V, Taroni F, Botti S, Lorenzetti D, Solari A et al (1996) Phenotypic heterogeneity in hereditary neuropathy with liability to pressure palsies associated with chromosome 17p11.2-12 deletion. Neurology 46:1133–1137

    Article  CAS  Google Scholar 

  7. Khedr EM, Fawi G, Allah Abbas MA, El-Fetoh NA, Zaki AF, Gamea A (2016) Prevalence of common types of compression neuropathies in Qena Governorate/Egypt: a population-based survey. Neuroepidemiology 46:253–260

    Article  Google Scholar 

  8. Van den Bergh PY, Haaden RD, Bouche P, Cornblath DR, Hahn A, Illa I et al (2010) European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society–first version. Eur J Neurol 17:356–363

    Article  Google Scholar 

  9. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy (2010) Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society-first revision. J Peripher Nerv Syst 15:295–301

    Article  Google Scholar 

  10. Ozel G, Maisonobe T, Guyant-Marechal L, Maltete D, Lefaucheur R (2018) Hereditary neuropathy with liability to pressure palsies mimicking chronic inflammatory demyelinating polyneuropathy. Rev Neurol 174:575–577

    Article  CAS  Google Scholar 

  11. Paprocka J, Kajor M, Jamroz E, Jezela-Stanek A, Seeman P, Marszal E (2006) Hereditary neuropathy with liability to pressure palsy. Folia Neuropathol 44:290–294

    PubMed  Google Scholar 

  12. Hong YH, Kim M, Kim HJ, Sung JJ, Kim SH, Lee KW (2003) Clinical and electrophysiologic features of HNPP patients with 17p11.2 deletion. Acta Neurol Scand 108:352–358

    Article  Google Scholar 

  13. Gabreels-Festen A, Wetering RV (1999) Human nerve pathology caused by different mutational mechanisms of the PMP22 gene. Ann NY Acad Sci 883:336–343

    Article  CAS  Google Scholar 

  14. Aarskog NK, Vedeler CA (2000) Real-time quantitative polymerase chain reaction. A new method that detects both the peripheral myelin protein 22 duplication in Charcot-Marie-Tooth type 1A disease and the peripheral myelin protein 22 deletion in hereditary neuropathy with liability to pressure palsies. Hum Genet 107:494–498

    Article  CAS  Google Scholar 

  15. Kim SM, Chung KW, Choi BO, Yoon ES, Choi JY, Park KD et al (2004) Hereditary neuropathy with liability to pressure palsies (HNPP) patients of Korean ancestry with chromosome 17p11.2-p12 deletion. Exp Mol Med 36:28–35

    Article  CAS  Google Scholar 

  16. Pareyson D, Solari A, Taroni F, Botti S, Fallica E, Scaioli V (1998) Detection of hereditary neuropathy with liability to pressure palsies among patients with acute painless mononeuropathy or plexopathy. Muscle Nerve 21:1686–1691

    Article  CAS  Google Scholar 

  17. Mariman ECM, Gabreels-Festen AAWM, van Beersum SEC, Valentijn LJ, Baas F, Bolhuis PA et al (1994) Prevalence of the 1.5-Mb 17p deletion in families with hereditary neuropathy with liability to pressure palsies. Ann Neurol 36:650–655

    Article  CAS  Google Scholar 

  18. Nelis E, Van Broeckhoven C, Jonghe P, Lofgren A, Vandenberghe A, Latour P (1996) Estimation of the mutation frequencies in Charcot-Marie-Tooth disease type 1 and hereditary neuropathy with liability to pressure palsies. A European collaborative study. Eur J Hum Genet 4:25–33

    Article  CAS  Google Scholar 

  19. Timmerman V, Rautenstrauss B, Reiter LT, Koeuth T, Löfgren A, Liehr T et al (1997) Detection of the CMT1A/HNPP recombination hotspot in unrelated patients of European descent. J Med Genet 34:43–49

    Article  CAS  Google Scholar 

  20. Murphy SM, Laura M, Fawcett K, Pandraud A, Liu YT, Davidson GL et al (2012) Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing. J Neurol Neurosurg Psychiatry 83:706–710

    Article  Google Scholar 

  21. Karadima G, Koutsis G, Raftopoulou M, Karletidi KM, Zambelis T, Karandreas N et al (2015) Mutational analysis of Greek patients with suspected hereditary neuropathy with liability to pressure palsies (HNPP): a 15-year experience. J Periph Nerv Sys 20:79–85

    Article  CAS  Google Scholar 

  22. Luigetti M, Del Grande A, Conte A, Lo Monaco M, Bisogni G, Romano A et al (2014) Clinical, neurophysiological and pathologic findings of HNPP patients with 17p12 deletion: a single-centre experience. J Neurol Sci 341:46–50

    Article  CAS  Google Scholar 

  23. Rajabally Y, Adams D, Latour P, Attarian S (2016) Hereditary and inflammatory neuropathies: a review of reported associations, mimics and misdiagnoses. J Neurol Neurosurg Psychiatry 87:1051–1060

    Article  Google Scholar 

  24. Gouider R, LeGuern E, Gugenheim M, Tardieu S, Maisonobe T, Léger JM et al (1995) Clinical, electrophysiologic, and molecular correlations in 13 families with hereditary neuropathy with liability to pressure palsies and a chromosome 17p11.2 deletion. Neurology 45:2018–2023

    Article  CAS  Google Scholar 

  25. Lenssen PP, Gabreels-Festen AA, Valentijn LJ, Jongen PJ, van Beersum SE, van Engelen BG et al (1998) Hereditary neuropathy with liability to pressure palsies. Phenotypic differences between patients with the common deletion and a PMP22 frame shift mutation. Brain 121:1451–1458

    Article  Google Scholar 

Download references

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department for Neuromuscular Disorders, Faculty of Medicine, Neurology Clinic, Clinical Center of Serbia, University of Belgrade, 6, Dr Subotic Street, 11000, Belgrade, Serbia

    Vukan Ivanovic, Marija Brankovic, Bogdan Bjelica, Aleksandra Kacar, Radoje Tubic, Milena Jankovic, Ana Marjanovic, Ivana Novakovic, Vidosava Rakocevic-Stojanovic & Stojan Peric

Authors
  1. Vukan Ivanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marija Brankovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bogdan Bjelica
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aleksandra Kacar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Radoje Tubic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Milena Jankovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ana Marjanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ivana Novakovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Vidosava Rakocevic-Stojanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Stojan Peric
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by VI, SP, RT, BB, MB. The first draft of the manuscript was written by VI and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Stojan Peric.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standards

All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

All persons gave their informed consent prior to their inclusion in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ivanovic, V., Brankovic, M., Bjelica, B. et al. Yield of the PMP22 deletion analysis in patients with compression neuropathies. J Neurol 267, 3617–3623 (2020). https://doi.org/10.1007/s00415-020-10052-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-020-10052-w

Keywords

Search

Navigation