Two Causes of Demyelinating Neuropathy in One Patient: CMT1A and POEMS Syndrome

Chahin, Nizar; Zeldenrust, Steven R.; Amrami, Kimberly K.; Engelstad, JaNean; James, P; Dyck, B.

doi:10.1017/s0317167100006892

Cited by 7 publications

(4 citation statements)

References 30 publications

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“…He had marked progression of demyelinating neuropathy and was found to have an M‐spike monoclonal protein, which led to the diagnosis of POEMS syndrome ( p olyneuropathy, o rganomegaly, e ndocrinology, M ‐spike, s kin changes). His nerve biopsy showed marked interstitial inflammation and supported the conclusion that an acquired process compounded his inherited demyelinating neuropathy . Through autologous peripheral blood stem cell transplantation, he went from wheelchair dependency to walking independently and returned to his prior deficit baseline from demyelinating neuropathy.…”

Section: Identification Of Inherited Neuropathiesmentioning

confidence: 59%

Inherited neuropathies: Clinical overview and update

2013

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Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests.

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Section: Identification Of Inherited Neuropathiesmentioning

confidence: 59%

Inherited neuropathies: Clinical overview and update

2013

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“…While the absence of conduction block and temporal dispersion are more suggestive of inherited demyelinating disorders, the conduction velocities are not slowed to the degree expected in CMT1. Also, the clinical features of POEMS suggest an acquired disorder with a rapidly progressive polyradiculoneuropathy in contrast with a lifelong progressive length dependent neuropathy typical of CMT1 16. Almost all of the different demyelinating components (conduction velocities, distal latencies, F wave latencies) were the same or slower than in CIDP.…”

Section: Discussionmentioning

confidence: 97%

Uniform demyelination and more severe axonal loss distinguish POEMS syndrome from CIDP

Mauermann

Sorenson

Dispenzieri

et al. 2012

J Neurol Neurosurg Psychiatry

122

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NCS/EMG of POEMS syndrome suggests both axonal loss and demyelination. Compared with CIDP, there is greater axonal loss (reduction of motor amplitudes and increased fibrillation potentials), greater slowing of the intermediate nerve segments, less common temporal dispersion and conduction block, and absent sural sparing. These findings imply that the pathology of POEMS syndrome is diffusely distributed (uniform demyelination) along the nerve where the pathology of CIDP is probably predominantly proximal and distal. Median motor TLI may be useful in clinically distinguishing these disorders.

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“…[5][6][7][8] One large prospective study indicated that as many as 42% of patients with previously undiagnosed polyneuropathy coming to tertiary care referral had familial occurrence.…”

Section: Discussionmentioning

confidence: 99%

Target-enrichment sequencing and copy number evaluation in inherited polyneuropathy

Wang

Dawson

et al. 2016

Neurology

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Objective: To assess the efficiency of target-enrichment next-generation sequencing (NGS) with copy number assessment in inherited neuropathy diagnosis.Methods: A 197 polyneuropathy gene panel was designed to assess for mutations in 93 patients with inherited or idiopathic neuropathy without known genetic cause. We applied our novel copy number variation algorithm on NGS data, and validated the identified copy number mutations using CytoScan (Affymetrix). Cost and efficacy of this targeted NGS approach was compared to earlier evaluations.Results: Average coverage depth was ;7603 (median 5 600, 99.4% . 1003). Among 93 patients, 18 mutations were identified in 17 cases (18%), including 3 copy number mutations: 2 PMP22 duplications and 1 MPZ duplication. The 2 patients with PMP22 duplication presented with bulbar and respiratory involvement and had absent extremity nerve conductions, leading to axonal diagnosis. Average onset age of these 17 patients was 25 years (2-61 years), vs 45 years for those without genetic discovery. Among those with onset age less than 40 years, the diagnostic yield of targeted NGS approach is high (27%) and cost savings is significant (;20%). However, the cost savings for patients with late onset age and without family history is not demonstrated. Conclusions:Incorporating copy number analysis in target-enrichment NGS approach improved the efficiency of mutation discovery for chronic, inherited, progressive length-dependent polyneuropathy diagnosis. The new technology is facilitating a simplified genetic diagnostic algorithm utilizing targeted NGS, clinical phenotypes, age at onset, and family history to improve diagnosis efficiency. Our findings prompt a need for updating the current practice parameters and payer guidelines. Neurology ® 2016;86:1762-1771 GLOSSARY CIAP 5 chronic idiopathic axonal polyneuropathy; CMT 5 Charcot-Marie-Tooth; CNV 5 copy number variation; DGV 5 Database of Genomic Variants; HMSN 5 hereditary motor and sensory polyneuropathy; MAF 5 minor allele frequency; NGS 5 next-generation sequencing; VUS 5 variants of unclear significance; WES 5 whole exome sequencing.Polyneuropathies are common, with overall prevalence of 1.7%, and 6.6% among persons over 60 years old.1 The high prevalence, multiple impairments, and complicated diagnostic procedures lead to high health care cost.1,2 Separating inherited from acquired causes is often difficult for insidious adult-onset cases, due to overlapping phenotypes.3,4 Furthermore, inherited and acquired polyneuropathies may coexist, resulting in worse severity. [5][6][7][8] One large prospective study indicated that as many as 42% of patients with previously undiagnosed polyneuropathy coming to tertiary care referral had familial occurrence. 9Pragmatic diagnostic strategies have long been sought to improve testing effectiveness and reduce costs in neuropathy diagnosis. [10][11][12] In Charcot-Marie-Tooth clinics, algorithms have been developed for selecting candidate genes.13 This approach is helpful for patients who have c...

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Two Causes of Demyelinating Neuropathy in One Patient: CMT1A and POEMS Syndrome

Cited by 7 publications

References 30 publications

Inherited neuropathies: Clinical overview and update

Inherited neuropathies: Clinical overview and update

Uniform demyelination and more severe axonal loss distinguish POEMS syndrome from CIDP

Target-enrichment sequencing and copy number evaluation in inherited polyneuropathy

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