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Semin Neurol
DOI: 10.1055/s-0044-1791520
Review Article

Top 10 Clinical Pearls in Inherited Neuropathies

Ruchee Patel
1   Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
,
Bipasha Mukherjee-Clavin
1   Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Abstract

The inherited neuropathies are a clinically and genetically heterogeneous collection of neuropathies that neurologists, particularly neuromuscular specialists, must be familiar with. They include Charcot–Marie–Tooth disease, which is common yet currently lacks targeted treatment, and hATTRV polyneuropathy, which is rare but has disease-modifying gene therapies. With a focus on emerging new genes and treatments, this article offers a recent update on clinical diagnosis and management of inherited neuropathies.

Keywords

inherited neuropathies - Charcot–Marie–Tooth disease - genetic neuropathy


Publication History

Article published online:
15 October 2024

© 2024. Thieme. All rights reserved.

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  • References

  • 1 Skre H. Genetic and clinical aspects of Charcot-Marie-Tooth's disease. Clin Genet 1974; 6 (02) 98-118
    CrossrefPubMedGoogle Scholar
  • 2 Cortese A, Zhu Y, Rebelo AP. et al; Inherited Neuropathy Consortium. Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Nat Genet 2020; 52 (05) 473-481
    CrossrefPubMedGoogle Scholar
  • 3 Ando Y, Coelho T, Berk JL. et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis 2013; 8 (01) 31
    CrossrefPubMedGoogle Scholar
  • 4 Cortese A, Vegezzi E, Lozza A. et al. Diagnostic challenges in hereditary transthyretin amyloidosis with polyneuropathy: avoiding misdiagnosis of a treatable hereditary neuropathy. J Neurol Neurosurg Psychiatry 2017; 88 (05) 457-458
    CrossrefPubMedGoogle Scholar
  • 5 Germain DP. Fabry disease. Orphanet J Rare Dis 2010; 5 (01) 30
    CrossrefPubMedGoogle Scholar
  • 6 Desnick RJ, Brady R, Barranger J. et al. Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 2003; 138 (04) 338-346
    CrossrefPubMedGoogle Scholar
  • 7 Mauer M, Wallace E, Schiffmann R. Fabry disease: clinical features and diagnosis. In: Curhan G, Glassock R. eds. Wolters Kluwer; . Updated July 20, 2023. Accessed February 25, 2024 at: https://medilib.ir/uptodate/show/7195
    Google Scholar
  • 8 Waldek S, Patel MR, Banikazemi M, Lemay R, Lee P. Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry. Genet Med 2009; 11 (11) 790-796
    CrossrefPubMedGoogle Scholar
  • 9 Mauer M, Wallace E, Schiffmann R. Fabry disease: treatment and prognosis. In: Curhan G, Glassock R. eds. Wolters Kluwer; . Updated November 27, 2023. Accessed February 25, 2024 at: https://fl-policies.exploremyplan.com/portal/web/fl-policies/home/-/asset_publisher/gvKEs0SDu27L/content/ph-0708/78515
    Google Scholar
  • 10 Laššuthová P, Mazanec R, Staněk D. et al. Biallelic variants in the SORD gene are one of the most common causes of hereditary neuropathy among Czech patients. Sci Rep 2021; 11 (01) 8443
    CrossrefPubMedGoogle Scholar
  • 11 Grosz BR, Stevanovski I, Negri S. et al. Long read sequencing overcomes challenges in the diagnosis of SORD neuropathy. J Peripher Nerv Syst 2022; 27 (02) 120-126
    CrossrefPubMedGoogle Scholar
  • 12 White A, Bontrager J, Laxen W. et al. P004: urine polyols for diagnosis of sorbitol dehydrogenase (SORD) deficiency-related peripheral neuropathy*. Genet Med Open 2024; 2: 100881
    CrossrefPubMedGoogle Scholar
  • 13 Furuta Y, Nelson ET, Neumann SM. et al; Undiagnosed Diseases Network. A medical odyssey of a 72-year-old man with Charcot-Marie-Tooth disease type 2 newly diagnosed with biallelic variants in SORD gene causing sorbitol dehydrogenase deficiency. Am J Med Genet A 2023; 191 (12) 2873-2877
    CrossrefPubMedGoogle Scholar
  • 14 Zhu Y, Lobato AG, Rebelo AP. et al. Sorbitol reduction via govorestat ameliorates synaptic dysfunction and neurodegeneration in sorbitol dehydrogenase deficiency. JCI Insight 2023; 8 (10) e164954
    CrossrefPubMedGoogle Scholar
  • 15 Klein CJ, Duan X, Shy ME. Inherited neuropathies: clinical overview and update. Muscle Nerve 2013; 48 (04) 604-622
    CrossrefPubMedGoogle Scholar
  • 16 Koeppen AH. Friedreich's ataxia: pathology, pathogenesis, and molecular genetics. J Neurol Sci 2011; 303 (1–2): 1-12
    CrossrefPubMedGoogle Scholar
  • 17 Opal P, Zoghbi H. Friedreich ataxia. In: Firth HV, Eichler AF. eds. UpToDate. Accessed February 25, 2025 at: https://www.uptodate.com/contents/autosomal-dominant-spinocerebellar-ataxias
    Google Scholar
  • 18 Child JS, Perloff JK, Bach PM, Wolfe AD, Perlman S, Kark RA. Cardiac involvement in Friedreich's ataxia: a clinical study of 75 patients. J Am Coll Cardiol 1986; 7 (06) 1370-1378
    CrossrefPubMedGoogle Scholar
  • 19 Payne RM, Wagner GR. Cardiomyopathy in Friedreich ataxia: clinical findings and research. J Child Neurol 2012; 27 (09) 1179-1186
    CrossrefPubMedGoogle Scholar
  • 20 Lynch DR, Chin MP, Delatycki MB. et al. Safety and efficacy of omaveloxolone in Friedreich ataxia (MOXIe Study). Ann Neurol 2021; 89 (02) 212-225
    CrossrefPubMedGoogle Scholar
  • 21 Lynch DR, Chin MP, Boesch S. et al. Efficacy of omaveloxolone in Friedreich's ataxia: delayed-start analysis of the MOXIe extension. Mov Disord 2023; 38 (02) 313-320
    CrossrefPubMedGoogle Scholar
  • 22 Manole A, Jaunmuktane Z, Hargreaves I. et al. Clinical, pathological and functional characterization of riboflavin-responsive neuropathy. Brain 2017; 140 (11) 2820-2837
    CrossrefPubMedGoogle Scholar
  • 23 Gorcenco S, Vaz FM, Tracewska-Siemiatkowska A. et al. Oral therapy for riboflavin transporter deficiency - what is the regimen of choice?. Parkinsonism Relat Disord 2019; 61: 245-247
    CrossrefPubMedGoogle Scholar
  • 24 Cortese A, Simone R, Sullivan R. et al. Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nat Genet 2019; 51 (04) 649-658
    CrossrefPubMedGoogle Scholar
  • 25 Beijer D, Dohrn MF, De Winter J. et al. RFC1 repeat expansions: a recurrent cause of sensory and autonomic neuropathy with cough and ataxia. Eur J Neurol 2022; 29 (07) 2156-2161
    CrossrefPubMedGoogle Scholar
  • 26 Paisán-Ruiz C, Jen JC. CANVAS with cerebellar/sensory/vestibular dysfunction from RFC1 intronic pentanucleotide expansion. Brain 2020; 143 (02) 386-390
    CrossrefPubMedGoogle Scholar
  • 27 Roberts RC. Removing the idiopathic from the chronic sensory neuropathies. Brain 2021; 144 (05) 1291-1292
    CrossrefPubMedGoogle Scholar
  • 28 Cortese A, Reilly MM, Houlden H. RFC1 CANVAS / Spectrum disorder. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2024. Updated November 25, 2020. Accessed February 25, 2024 at: https://www.ncbi.nlm.nih.gov/books/NBK564656/.
    PubMed
  • 29 Pipis M, Rossor AM, Laura M, Reilly MM. Next-generation sequencing in Charcot-Marie-Tooth disease: opportunities and challenges. Nat Rev Neurol 2019; 15 (11) 644-656
    CrossrefPubMedGoogle Scholar
  • 30 Fridman V, Bundy B, Reilly MM. et al; Inherited Neuropathies Consortium. CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis. J Neurol Neurosurg Psychiatry 2015; 86 (08) 873-878
    CrossrefPubMedGoogle Scholar
  • 31 Li J, Parker B, Martyn C, Natarajan C, Guo J. The PMP22 gene and its related diseases. Mol Neurobiol 2013; 47 (02) 673-698
    CrossrefPubMedGoogle Scholar
  • 32 Liu X, Duan X, Zhang Y, Fan D. Clinical and genetic diversity of PMP22 mutations in a large cohort of Chinese patients with Charcot-Marie-Tooth disease. Front Neurol 2020; 11: 630
    CrossrefPubMedGoogle Scholar
  • 33 Abrams CK. GJB1 disorders: Charcot-Marie-Tooth neuropathy (CMT1X) and central nervous system phenotypes. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Updated April 25, 2024. Originally published June 18, 1998. Accessed February 25, 2024 at: https://www.ncbi.nlm.nih.gov/books/NBK1374/
    PubMed
  • 34 Sargiannidou I, Vavlitou N, Aristodemou S. et al. Connexin32 mutations cause loss of function in Schwann cells and oligodendrocytes leading to PNS and CNS myelination defects. J Neurosci 2009; 29 (15) 4736-4749
    CrossrefPubMedGoogle Scholar
  • 35 Shy ME, Jáni A, Krajewski K. et al. Phenotypic clustering in MPZ mutations. Brain 2004; 127 (Pt 2): 371-384
    CrossrefPubMedGoogle Scholar
  • 36 Feely SME, Laura M, Siskind CE. et al. MFN2 mutations cause severe phenotypes in most patients with CMT2A; 2011. Accessed September 16, 2024 at: www.neurology.org
    PubMed
  • 37 Pipis M, Feely SME, Polke JM. et al; Inherited Neuropathies Consortium - Rare Disease Clinical Research Network (INC-RDCRN). Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study. Brain 2020; 143 (12) 3589-3602
    CrossrefPubMedGoogle Scholar
  • 38 Zhou Y, Carmona S, Muhammad AKMG. et al. Restoring mitofusin balance prevents axonal degeneration in a Charcot-Marie-Tooth type 2A model. J Clin Invest 2019; 129 (04) 1756-1771
    CrossrefPubMedGoogle Scholar
  • 39 Phillips KA, Trosman JR, Douglas MP. et al. US private payers' perspectives on insurance coverage for genome sequencing versus exome sequencing: a study by the Clinical Sequencing Evidence-Generating Research Consortium (CSER). Genet Med 2022; 24 (01) 238-244
    CrossrefPubMedGoogle Scholar
  • 40 Pfeffer GB, Gonzalez T, Brodsky J. et al. A consensus statement on the surgical treatment of Charcot-Marie-Tooth disease. Foot Ankle Int 2020; 41 (07) 870-880
    CrossrefPubMedGoogle Scholar
  • 41 Waldman LE, Michalski MP, Giaconi JC, Pfeffer GB, Learch TJ. Charcot-Marie-Tooth disease of the foot and ankle: imaging features and pathophysiology. Radiographics 2023; 43 (04) e220114
    CrossrefPubMedGoogle Scholar
  • 42 Guccione AA, Peteet JO. Standing wedge for increasing ankle dorsiflexion. Phys Ther 1979; 59 (06) 766-767
    CrossrefPubMedGoogle Scholar
  • 43 Conde RM, Senem I, Dos Santos M, de Lima Osório F, Marques Júnior W. Effectiveness of exercise therapy for individuals diagnosed with Charcot-Marie-Tooth disease: a systematic review of randomized clinical trials. J Peripher Nerv Syst 2023; 28 (02) 169-178
    CrossrefPubMedGoogle Scholar
  • 44 Sman AD, Hackett D, Fiatarone Singh M, Fornusek C, Menezes MP, Burns J. Systematic review of exercise for Charcot-Marie-Tooth disease. J Peripher Nerv Syst 2015; 20 (04) 347-362
    CrossrefPubMedGoogle Scholar
  • 45 Burns J, Sman AD, Cornett KMD. et al; FAST Study Group. Safety and efficacy of progressive resistance exercise for Charcot-Marie-Tooth disease in children: a randomised, double-blind, sham-controlled trial. Lancet Child Adolesc Health 2017; 1 (02) 106-113
    CrossrefPubMedGoogle Scholar
  • 46 Raikin SM, Parks BG, Noll KH, Schon LC. Biomechanical evaluation of the ability of casts and braces to immobilize the ankle and hindfoot. Foot Ankle Int 2001; 22 (03) 214-219
    CrossrefPubMedGoogle Scholar
  • 47 Valeria P, Schizzi S, Poggi I. et al. Hand rehabilitation treatment for Charcot-Marie-Tooth disease: an open label pilot study. J Neurol Neurophysiol 2018; 09 (04) 465
    CrossrefPubMedGoogle Scholar
  • 48 Dimeglio A, Canavese F. Progression or not progression? How to deal with adolescent idiopathic scoliosis during puberty. J Child Orthop 2013; 7 (01) 43-49
    CrossrefPubMedGoogle Scholar
  • 49 Karol LA, Elerson E. Scoliosis in patients with Charcot-Marie-Tooth disease. J Bone Joint Surg Am 2007; 89 (07) 1504-1510
    CrossrefPubMedGoogle Scholar
  • 50 McKinney JL, Islam MP. Neurophysiologic intraoperative monitoring (NIOM) in pediatric patients with polyneuropathy. Childs Nerv Syst 2020; 36 (11) 2801-2805
    CrossrefPubMedGoogle Scholar
  • 51 McCorquodale D, Pucillo EM, Johnson NE. Management of Charcot-Marie-Tooth disease: improving long-term care with a multidisciplinary approach. J Multidiscip Healthc 2016; 9: 7-19
    PubMedGoogle Scholar
  • 52 Cavaletti G, Forsey K, Alberti P. Toxic medications in Charcot-Marie-Tooth patients: a systematic review. J Peripher Nerv Syst 2023; 28 (03) 295-307
    CrossrefPubMedGoogle Scholar
  • 53 Eichinger K, Sowden JE, Burns J. et al. Accelerate clinical trials in Charcot-Marie-Tooth disease (ACT-CMT): a protocol to address clinical trial readiness in CMT1A. Front Neurol 2022; 13: 930435
    CrossrefPubMedGoogle Scholar
  • 54 Zhao HT, Damle S, Ikeda-Lee K. et al. PMP22 antisense oligonucleotides reverse Charcot-Marie-Tooth disease type 1A features in rodent models. J Clin Invest 2018; 128 (01) 359-368
    CrossrefPubMedGoogle Scholar
  • 55 Shy ME. Antisense oligonucleotides offer hope to patients with Charcot-Marie-Tooth disease type 1A. J Clin Invest 2018; 128 (01) 110-112
    CrossrefPubMedGoogle Scholar
  • 56 Brooks PJ, Miller TM, Revah F. et al; The Bespoke Gene Therapy Consortium. The Bespoke Gene Therapy Consortium: facilitating development of AAV gene therapies for rare diseases. Nat Rev Drug Discov 2024; 23 (03) 157-158
    CrossrefPubMedGoogle Scholar