Overview of hereditary neuropathies
- Peter B Kang, MD, FAAP, FAAN
Peter B Kang, MD, FAAP, FAAN
- Chief, Division of Pediatric Neurology and Associate Professor of Pediatrics
- University of Florida College of Medicine
- Section Editors
- Jeremy M Shefner, MD, PhD
Jeremy M Shefner, MD, PhD
- Section Editor — Neuromuscular Disease
- Professor and Chair of Neurology, Barrow Neurological Institute
- Professor of Neurology, University of Arizona, Phoenix
- Clinical Professor of Neurology, Creighton University
- Douglas R Nordli, Jr, MD
Douglas R Nordli, Jr, MD
- Section Editor — Pediatric Neurology
- Chief of Neurology
- Children’s Hospital Los Angeles
- Vice Chair of Neurology
- USC Keck School of Medicine
The hereditary peripheral neuropathies have been classified based upon clinical characteristics, mode of inheritance, electrophysiologic features, metabolic defect, and subsequently upon specific genetic loci. The primary hereditary neuropathies predominantly or exclusively affect peripheral nerves and produce symptoms of peripheral nerve dysfunction. Other hereditary neuropathies affect both the central and peripheral nervous systems and, in some cases, other organs; in such patients, symptoms related to the peripheral neuropathy may be overshadowed by other manifestations of the disease.
This topic will provide an overview of the hereditary neuropathies. Detailed discussions are found separately. (See "Hereditary primary motor sensory neuropathies, including Charcot-Marie-Tooth disease" and "Hereditary sensory and autonomic neuropathies" and "Neuropathies associated with hereditary disorders".)
Historically, the primary hereditary neuropathies were designated by eponyms that had the connotation of specific clinical features (eg, Charcot-Marie-Tooth [CMT] disease or Dejerine-Sottas disease). However, phenotypic variability resulted in substantial diagnostic confusion. The Dyck classification developed in the 1970s helped to define specific types based upon clinical and electrophysiologic features , though the popularity of the CMT eponym has had a resurgence since the 1990s, specifically for hereditary motor sensory neuropathies, especially as a more comprehensive classification tree based on associated genes has been built upon the original broad CMT categories that were based largely on inheritance patterns and neurophysiology.
●Many of the primary hereditary neuropathies are divided into motor-sensory (CMT) and sensory-autonomic neuropathies.
●The motor-sensory category was subdivided into types 1 through 7 and the sensory neuropathies into types 1 through 5. Many of these types were further divided into subcategories.
- Dyck PJ. Neuronal atrophy and degeneration predominantly affecting peripheral sensory and autonomic neurons. In: Peripheral Neuropathy, Dyck PJ, Thomas PK, Lambert EH, et al (Eds), WB Saunders, Philadelphia 1984. Vol 2.
- Fridman V, Murphy SM. The spectrum of axonopathies: from CMT2 to HSP. Neurology 2014; 83:580.
- Klein CJ, Middha S, Duan X, et al. Application of whole exome sequencing in undiagnosed inherited polyneuropathies. J Neurol Neurosurg Psychiatry 2014; 85:1265.
- Liu YT, Laurá M, Hersheson J, et al. Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy. Neurology 2014; 83:612.
- Saporta AS, Sottile SL, Miller LJ, et al. Charcot-Marie-Tooth disease subtypes and genetic testing strategies. Ann Neurol 2011; 69:22.
- Gabreëls-Festen AA, Gabreëls FJ, Joosten EM, et al. Hereditary neuropathy with liability to pressure palsies in childhood. Neuropediatrics 1992; 23:138.
- Mouton P, Tardieu S, Gouider R, et al. Spectrum of clinical and electrophysiologic features in HNPP patients with the 17p11.2 deletion. Neurology 1999; 52:1440.
- Potulska-Chromik A, Sinkiewicz-Darol E, Ryniewicz B, et al. Clinical, electrophysiological, and molecular findings in early onset hereditary neuropathy with liability to pressure palsy. Muscle Nerve 2014; 50:914.
- Korn-Lubetzki I, Argov Z, Raas-Rothschild A, et al. Family with inflammatory demyelinating polyneuropathy and the HNPP 17p12 deletion. Am J Med Genet 2002; 113:275.
- Luigetti M, Del Grande A, Conte A, et al. Clinical, neurophysiological and pathological findings of HNPP patients with 17p12 deletion: a single-centre experience. J Neurol Sci 2014; 341:46.
- Yilmaz U, Bird TT, Carter GT, et al. Pain in hereditary neuropathy with liability to pressure palsy: an association with fibromyalgia syndrome? Muscle Nerve 2015; 51:385.
- Choi YH, Dunn B. Low back pain with radicular symptoms as a presentation of hereditary neuropathy with liability to pressure palsies: the diagnostic challenge of an atypical presentation. Muscle Nerve 2016; 53:655.
- Sanahuja J, Franco E, Rojas-García R, et al. 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.
- Tackenberg B, Möller JC, Rindock H, et al. CNS involvement in hereditary neuropathy with pressure palsies (HNPP). Neurology 2006; 67:2250.
- Andersson PB, Yuen E, Parko K, So YT. Electrodiagnostic features of hereditary neuropathy with liability to pressure palsies. Neurology 2000; 54:40.
- Meier C, Moll C. Hereditary neuropathy with liability to pressure palsies. Report of two families and review of the literature. J Neurol 1982; 228:73.
- Stögbauer F, Young P, Kuhlenbäumer G, et al. Hereditary recurrent focal neuropathies: clinical and molecular features. Neurology 2000; 54:546.
- Mariman EC, Gabreëls-Festen AA, van Beersum SE, et al. Prevalence of the 1.5-Mb 17p deletion in families with hereditary neuropathy with liability to pressure palsies. Ann Neurol 1994; 36:650.
- Bird TD. Hereditary neuropathy with liability to pressure palsies. GeneReviews. www.ncbi.nlm.nih.gov/books/NBK1392/ (Accessed on December 07, 2011).
- Li J, Ghandour K, Radovanovic D, et al. Stoichiometric alteration of PMP22 protein determines the phenotype of hereditary neuropathy with liability to pressure palsies. Arch Neurol 2007; 64:974.
- Infante J, García A, Combarros O, et al. Diagnostic strategy for familial and sporadic cases of neuropathy associated with 17p11.2 deletion. Muscle Nerve 2001; 24:1149.
- Guo J, Wang L, Zhang Y, et al. Abnormal junctions and permeability of myelin in PMP22-deficient nerves. Ann Neurol 2014; 75:255.
- Kuhlenbäumer G, Timmerman V. Giant axonal neuropathy. GeneReviews. www.ncbi.nlm.nih.gov/books/NBK1136/ (Accessed on December 07, 2011).
- Johnson-Kerner BL, Roth L, Greene JP, et al. Giant axonal neuropathy: An updated perspective on its pathology and pathogenesis. Muscle Nerve 2014; 50:467.
- Takebe Y, Koide N, Takahashi G. Giant axonal neuropathy: report of two siblings with endocrinological and histological studies. Neuropediatrics 1981; 12:392.
- Ben Hamida C, Cavalier L, Belal S, et al. Homozygosity mapping of giant axonal neuropathy gene to chromosome 16q24.1. Neurogenetics 1997; 1:129.
- Bomont P, Cavalier L, Blondeau F, et al. The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy. Nat Genet 2000; 26:370.
- Flanigan KM, Crawford TO, Griffin JW, et al. Localization of the giant axonal neuropathy gene to chromosome 16q24. Ann Neurol 1998; 43:143.
- Mohri I, Taniike M, Yoshikawa H, et al. A case of giant axonal neuropathy showing focal aggregation and hypophosphorylation of intermediate filaments. Brain Dev 1998; 20:594.
- Mussche S, De Paepe B, Smet J, et al. Proteomic analysis in giant axonal neuropathy: new insights into disease mechanisms. Muscle Nerve 2012; 46:246.
- Demir E, Bomont P, Erdem S, et al. Giant axonal neuropathy: clinical and genetic study in six cases. J Neurol Neurosurg Psychiatry 2005; 76:825.
- Incecik F, Herguner OM, Ceylaner S, et al. Giant axonal disease: Report of eight cases. Brain Dev 2015; 37:803.
- Dooley JM, Oshima Y, Becker LE, Murphy EG. Clinical progression of giant-axonal neuropathy over a twelve year period. Can J Neurol Sci 1981; 8:321.
- Majnemer A, Rosenblatt B, Watters G, Andermann F. Giant axonal neuropathy: central abnormalities demonstrated by evoked potentials. Ann Neurol 1986; 19:394.
- Carpenter S, Karpati G, Andermann F, Gold R. Giant axonal neuropathy. A clinically and morphologically distinct neurological disease. Arch Neurol 1974; 31:312.
- Treiber-Held S, Budjarjo-Welim H, Reimann D, et al. Giant axonal neuropathy: a generalized disorder of intermediate filaments with longitudinal grooves in the hair. Neuropediatrics 1994; 25:89.
- HEREDITARY MOTOR AND SENSORY NEUROPATHIES
- HEREDITARY NEUROPATHY WITH LIABILITY TO PRESSURE PALSY
- HEREDITARY BRACHIAL PLEXOPATHY
- HEREDITARY SENSORY AND AUTONOMIC NEUROPATHIES
- GIANT AXONAL NEUROPATHY
- NEUROPATHIES ASSOCIATED WITH GENERALIZED DISORDERS
- INFORMATION FOR PATIENTS