Paeds · neurology-neurodisability-and-neuromuscular

Peripheral neuropathies

Also known as Charcot-Marie-Tooth disease · CMT · Hereditary motor and sensory neuropathy · HMSN · Chronic inflammatory demyelinating polyneuropathy · CIDP · Hereditary neuropathy with liability to pressure palsies · HNPP

Fellowship guide to peripheral neuropathies in children covering the inherited and acquired polyneuropathies. Details Charcot-Marie-Tooth disease subtypes CMT1A with PMP22 duplication, CMT1B with MPZ, CMT2A with MFN2, CMTX1 with GJB1 connexin 32, and HNPP with PMP22 deletion, the clinical phenotype of distal wasting with pes cavus and foot drop, the nerve conduction study distinction between demyelinating under thirty-eight metres per second and axonal patterns, the paediatric CMT clinical practice guideline of Yiu 2022, the acquired neuropathies including chronic inflammatory demyelinating polyradiculoneuropathy with its greater than eight weeks criterion and treatment with intravenous immunoglobulin and corticosteroids, diabetic neuropathy in youth, chemotherapy-induced and vincristine neuropathy that can unmask Charcot-Marie-Tooth disease, and the multidisciplinary management with orthotics, physiotherapy, foot surgery, pain control, and genetic counselling.

high11 referencesUpdated 16 July 202626 min readVerification in progress

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Red flags

A child receiving vincristine for leukaemia who develops severe acute neuropathy may have undiagnosed Charcot-Marie-Tooth disease; check for pes cavus and family history before the first dose, because vincristine can cause irreversible paralysis in CMTProgressive symmetric weakness over more than eight weeks with areflexia and demyelinating nerve conduction studies is chronic inflammatory demyelinating polyradiculoneuropathy until proven otherwise, not a slow Guillain-Barre syndrome, and it responds to corticosteroids unlike Guillain-Barre syndromeA child with pes cavus, hammer toes, and distal leg wasting almost certainly has an inherited neuropathy, and the single most useful bedside question is whether anyone in the family has high arches, foot drop, or abnormal gaitRecurrent painless focal palsies after minor compression, such as wrist drop after leaning on a desk, point to hereditary neuropathy with liability to pressure palsies from a PMP22 deletionMedian motor nerve conduction velocity under thirty-eight metres per second with uniform slowing across all nerves distinguishes CMT1 demyelinating disease from acquired demyelination, which shows patchy non-uniform conduction block

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Recognises Charcot-Marie-Tooth disease as the commonest inherited neuropathy of childhood with prevalence around one in two thousand five hundred and describes the phenotype of distal wasting, pes cavus, foot drop, and areflexiaStates that CMT1A is caused by a PMP22 duplication on chromosome seventeen and that nerve conduction velocity under thirty-eight metres per second indicates a demyelinating neuropathyIdentifies that chronic inflammatory demyelinating polyradiculoneuropathy progresses over more than eight weeks and responds to corticosteroids and intravenous immunoglobulin unlike Guillain-Barre syndromeDistinguishes the demyelinating CMT1 with uniform slowing from the axonal CMT2 and the X-linked CMTX1 with GJB1 connexin 32 variants using nerve conduction studies and targeted genetic testingApplies the Yiu 2022 paediatric Charcot-Marie-Tooth clinical practice guideline for orthotic, surgical, and rehabilitation management and recognises that no disease-modifying therapy has proven effective for CMT1ARecognises that vincristine can unmask or severely worsen Charcot-Marie-Tooth disease and that genetic neuropathies can present with chronic inflammatory demyelinating polyradiculoneuropathy-like features in childhoodThe Charcot-Marie-Tooth classification into demyelinating CMT1, axonal CMT2, and intermediate types with their major genes PMP22, MPZ, MFN2, and GJB1The nerve conduction study distinction: uniform slowing under thirty-eight metres per second for CMT1 versus reduced amplitudes with preserved velocity for CMT2The chronic inflammatory demyelinating polyradiculoneuropathy criterion of progression over more than eight weeks and its treatment with intravenous immunoglobulin, corticosteroids, and plasma exchangeAssesses a child with progressive distal weakness and foot deformity, interprets nerve conduction studies, and constructs a multidisciplinary management plan with orthotics, physiotherapy, and genetic counsellingDistinguishes hereditary from acquired neuropathy using the family history, the tempo, the symmetry, and the nerve conduction pattern, and identifies treatable acquired causesCounsels the family on inheritance, prognosis, the role of genetic testing, and the implications for anaesthesia and chemotherapy including the vincristine contraindication in Charcot-Marie-Tooth diseaseLevel 1: Recognition that pes cavus, distal leg wasting, and areflexia in a child suggest an inherited neuropathy and that a family history of foot deformity strengthens the diagnosisLevel 2: Application of nerve conduction studies to distinguish demyelinating from axonal neuropathy and knowledge of the common Charcot-Marie-Tooth genesLevel 3: Multidisciplinary management using the paediatric guideline, identification of treatable acquired neuropathies, and genetic counselling including reproductive implicationsCharcot-Marie-Tooth disease as the commonest inherited neuromuscular disorder with CMT1A from PMP22 duplication causing demyelination and CMT2A from MFN2 causing axonal diseaseThe nerve conduction velocity threshold of thirty-eight metres per second to separate demyelinating from axonal neuropathy and the concept of uniform versus patchy slowingChronic inflammatory demyelinating polyradiculoneuropathy as an acquired treatable neuropathy progressing over more than eight weeks, responsive to corticosteroids and intravenous immunoglobulinExamination of the feet, gait, reflexes, and sensation in a child with suspected neuropathy, and the identification of pes cavus, hammer toes, and distal wastingInterpretation of nerve conduction studies and targeted genetic testing, and the construction of a management plan with ankle-foot orthoses and physiotherapyCommunication of the diagnosis, inheritance pattern, prognosis, and the need to avoid vincristine in Charcot-Marie-Tooth diseaseCharcot-Marie-Tooth disease as the commonest inherited peripheral neuropathy in United States children with autosomal dominant CMT1A from PMP22 duplicationThe clinical features of distal muscle wasting, pes cavus, foot drop, steppage gait, and impaired proprioception and vibration with relative sparing of pain and temperatureThe acquired neuropathies including chronic inflammatory demyelinating polyradiculoneuropathy, diabetic neuropathy, and chemotherapy-induced peripheral neuropathy from vincristineRecognition of the inherited neuropathy phenotype and the role of family history and nerve conduction studies in classificationIdentification of treatable acquired neuropathies including chronic inflammatory demyelinating polyradiculoneuropathy and diabetic neuropathy in youthThe vincristine precaution in suspected Charcot-Marie-Tooth disease and the multidisciplinary management with orthotics, physiotherapy, and surgeryCanadian approach to the classification and genetic diagnosis of Charcot-Marie-Tooth disease using nerve conduction studies and next-generation sequencing panelsThe distinction between hereditary uniform slowing and acquired patchy demyelination on nerve conduction studiesManagement using the paediatric guideline with ankle-foot orthoses, surgical correction, and genetic counselling, and the recognition of treatable acquired neuropathies

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Life stages

infanttoddlerpreschoolschool-ageadolescentyoung-adult-transition

Care settings

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Overview & Definition

A child who walks on the outer edges of high-arched feet, trips over unseen kerbs, and cannot feel the vibration of a tuning fork is showing one of the most recognisable patterns in paediatric neurology. Peripheral neuropathy is a disorder of the peripheral nerves, the motor, sensory, and autonomic fibres that connect the spinal cord to the limbs and the trunk, and in childhood it divides cleanly into the inherited and the acquired. The inherited family is dominated by Charcot-Marie-Tooth disease, the commonest inherited neuromuscular disorder of humans, with a prevalence of around one in two thousand five hundred. The acquired family is dominated by the treatable immune neuropathies, the toxic and metabolic neuropathies, and diabetic neuropathy in youth. [1]

The reason this topic matters above all is that the two families demand opposite management. The inherited neuropathies progress slowly over years, have no disease-modifying therapy, and are managed with orthotics, physiotherapy, foot surgery, pain control, and genetic counselling. The acquired neuropathies can progress over weeks and are treatable with immunoglobulin, corticosteroids, or removal of the offending drug or toxin. Confusing the two wastes the child's time and the family's hope, because a treatable CIDP mislabelled as Charcot-Marie-Tooth disease goes untreated while an incurable CMT given immunoglobulin gains nothing. [1][8]

The single concept that frames the whole topic is the nerve conduction study, which tells you whether the problem is the myelin or the axon. A motor conduction velocity under thirty-eight metres per second with uniform slowing across all nerves points to an inherited demyelinating disease, the CMT1 family. A velocity above thirty-eight with reduced amplitudes points to axonal disease, the CMT2 family. Patchy, non-uniform slowing with conduction block points to an acquired demyelinating process, the CIDP family. That one number, thirty-eight metres per second, sorts the disease at the bedside and drives the entire workup. [1]

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References11Show ledger

[1]Pareyson D, Marchesi C Diagnosis, natural history, and management of Charcot-Marie-Tooth disease. Lancet Neurol, 2009.PMID 19539237
[2]Lupski JR, de Oca-Luna RM, Slaugenhaupt S, et al DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell, 1991.PMID 1677316
[3]Chance PF, Alderson MK, Leppig KA, et al DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell, 1993.PMID 8422677
[4]Pipis M, Feely SME, Polke JM, et al Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study. Brain, 2020.PMID 33415332
[5]Record CJ, Skorupinska M, Laura M, et al Genetic analysis and natural history of Charcot-Marie-Tooth disease CMTX1 due to GJB1 variants. Brain, 2023.PMID 37284795
[6]Yiu EM, Bray P, Baets J, et al Clinical practice guideline for the management of paediatric Charcot-Marie-Tooth disease. J Neurol Neurosurg Psychiatry, 2022.PMID 35140138
[7]Fridman V, Bundy B, Reilly MM, et al 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.PMID 25430934
[8]Bunschoten C, Jacobs BC, Van den Bergh PYK, et al Progress in diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy. Lancet Neurol, 2019.PMID 31076244
[9]Fernandez-Garcia MA, Stettner GM, Kinali M, et al Genetic neuropathies presenting with CIDP-like features in childhood. Neuromuscul Disord, 2021.PMID 33386210
[10]Jaiswal M, Divers J, Dabelea D, et al Prevalence of and risk factors for diabetic peripheral neuropathy in youth with type 1 and type 2 diabetes. Diabetes Care, 2017.PMID 28674076
[11]Bjornard KL, Gilchrist LS, Inaba H, et al Peripheral neuropathy in children and adolescents treated for cancer. Lancet Child Adolesc Health, 2018.PMID 30236383

Peripheral neuropathies

high11 referencesUpdated 16 July 202626 min readVerification in progress

Practise this topic

Overview & Definition

Paediatrics Fellowship Pro

You have read the opening of this topic. The complete unit — every section and its primary-source references — is part of the Paediatrics Fellowship fellowship atlas.

References11Show ledger

[1]Pareyson D, Marchesi C Diagnosis, natural history, and management of Charcot-Marie-Tooth disease. Lancet Neurol, 2009.PMID 19539237
[2]Lupski JR, de Oca-Luna RM, Slaugenhaupt S, et al DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell, 1991.PMID 1677316
[3]Chance PF, Alderson MK, Leppig KA, et al DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell, 1993.PMID 8422677
[4]Pipis M, Feely SME, Polke JM, et al Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study. Brain, 2020.PMID 33415332
[5]Record CJ, Skorupinska M, Laura M, et al Genetic analysis and natural history of Charcot-Marie-Tooth disease CMTX1 due to GJB1 variants. Brain, 2023.PMID 37284795
[6]Yiu EM, Bray P, Baets J, et al Clinical practice guideline for the management of paediatric Charcot-Marie-Tooth disease. J Neurol Neurosurg Psychiatry, 2022.PMID 35140138
[7]Fridman V, Bundy B, Reilly MM, et al 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.PMID 25430934
[8]Bunschoten C, Jacobs BC, Van den Bergh PYK, et al Progress in diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy. Lancet Neurol, 2019.PMID 31076244
[9]Fernandez-Garcia MA, Stettner GM, Kinali M, et al Genetic neuropathies presenting with CIDP-like features in childhood. Neuromuscul Disord, 2021.PMID 33386210
[10]Jaiswal M, Divers J, Dabelea D, et al Prevalence of and risk factors for diabetic peripheral neuropathy in youth with type 1 and type 2 diabetes. Diabetes Care, 2017.PMID 28674076
[11]Bjornard KL, Gilchrist LS, Inaba H, et al Peripheral neuropathy in children and adolescents treated for cancer. Lancet Child Adolesc Health, 2018.PMID 30236383