Hereditary Neuropathies: Update 2017

AbstractHereditary neuropathy is an umbrella term for a group of nonsyndromic conditions with a prevalence of approximately 1:2,500. In addition to the most frequent form, Charcot–Marie–Tooth's disease (CMT, or hereditary motor and sensory neuropathy), there are additional entities such as hereditary neuropathy with liability to pressure palsies (HNPP), hereditary motor neuropathies (HMNs), and hereditary sensory and autonomic neuropathies (HSANs). With the exception of HNPP, which is almost always caused by defects of the PMP22 gene, all other forms show genetic heterogeneity with altogether close to 100 genes involved. Mutation detection rates vary considerably, reaching up to 80% in demyelinating CMT (CMT1) but are still as low as 10 to 30% in axonal CMT (CMT2), HMN, and HSAN. Based on current information, analysis of only four genes (PMP22, GJB1, MPZ, MFN2) identifies 80 to 90% of CMT-causing mutations that can be detected in all known disease genes. For the remaining patients, parallel analysis of multiple neuropathy genes using next-generation sequencing is now replacing phenotype-oriented multistep gene-by-gene sequencing. Such approaches tend to generate a wealth of genetic information that requires comprehensive evaluation of the pathogenic relevance of identified variants. In this review, we present current classification systems, specific phenotypic clues, and genetic testing algorithms in the different subgroups of hereditary neuropathies.

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Charcot-Marie-Tooth disease and hereditary motor neuropathies – Update 2020

Medizinische Genetik ◽

10.1515/medgen-2020-2038 ◽

2020 ◽

Vol 32 (3) ◽

pp. 207-219

Author(s):

Sabine Rudnik-Schöneborn ◽

Michaela Auer-Grumbach ◽

Jan Senderek

Keyword(s):

Comprehensive Evaluation ◽

Sensory Neuropathy ◽

Classification Systems ◽

Disease Genes ◽

Hereditary Neuropathy ◽

Detection Rates ◽

Charcot Marie Tooth ◽

Hereditary Motor ◽

Charcot Marie Tooth Disease ◽

Tooth Disease

Abstract Inherited peripheral neuropathy is the most common hereditary neuromuscular disease with a prevalence of about 1:2,500. The most frequent form is Charcot-Marie-Tooth disease (CMT, or hereditary motor and sensory neuropathy [HMSN]). Other clinical entities are hereditary neuropathy with liability to pressure palsies (HNPP), distal hereditary motor neuropathies (dHMN), and hereditary sensory and autonomic neuropathies (HSAN). With the exception of HNPP, which is almost always caused by defects of the PMP22 gene, all other forms show genetic heterogeneity with altogether more than 100 genes involved. Mutation detection rates vary considerably, reaching up to 80 % in demyelinating CMT (CMT1) but are still as low as 10–30 % in axonal CMT (CMT2), dHMN, and HSAN. Based on current information, analysis of only four genes (PMP22, GJB1, MPZ, MFN2) identifies 80–90 % of CMT-causing mutations that can be detected in all known disease genes. For the remaining patients, parallel analysis of multiple neuropathy genes using next-generation sequencing is now replacing phenotype-oriented multistep gene-by-gene sequencing. Such approaches tend to generate a wealth of genetic information that requires comprehensive evaluation of the pathogenic relevance of identified variants. In this review, we present current classification systems, specific phenotypic clues, and diagnostic yields in the different subgroups of hereditary CMT and motor neuropathies.

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Hereditary neuropathy with a liability to pressure palsies presenting as a case of sensory neuropathy following spinal anaesthesia for caesarean delivery

International Journal of Obstetric Anesthesia ◽

10.1016/j.ijoa.2010.07.005 ◽

2011 ◽

Vol 20 (1) ◽

pp. 95-96 ◽

Cited By ~ 2

Author(s):

R.J. Chilvers ◽

M.M. Salman

Keyword(s):

Spinal Anaesthesia ◽

Caesarean Delivery ◽

Sensory Neuropathy ◽

Hereditary Neuropathy ◽

Pressure Palsies

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Facial Paresthesia, a Rare Manifestation of Hereditary Neuropathy With Liability to Pressure Palsies: A Case Report

Frontiers in Neurology ◽

10.3389/fneur.2021.726437 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lisa De Kock ◽

Fréderic Van der Cruyssen ◽

Leonore Gruijthuijsen ◽

Constantinus Politis

Keyword(s):

Peripheral Nerves ◽

Case Reports ◽

Cranial Nerves ◽

Sensory Neuropathy ◽

Rare Condition ◽

Hereditary Neuropathy ◽

Rare Manifestation ◽

Facial Numbness ◽

Pressure Palsies ◽

Objective Tests

Trigeminal sensory neuropathy can be caused by a variety of conditions, including local, traumatic, iatrogenic, or systemic causes. Diagnosis and management remain a challenge for maxillofacial surgeons and neurologists. Therefore, a good clinical examination and objective tests and imaging are needed when diagnosing patients who present with facial numbness. We present a case with spontaneous episodes of facial paresthesia. He was diagnosed with hereditary neuropathy with liability to pressure palsies (HNPP), a rare condition that affects the peripheral nerves. Only a few case reports that describe involvement of the cranial nerves in patients with HNPP were found in the literature, and facial paresthesia has not been previously reported.

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Clinical, Electrophysiological and Molecular Features in Hereditary Neuropathy with Liability to Pressure Palsies

Sinapse ◽

10.46531/sinapse/ao/200055/2020 ◽

2020 ◽

Vol 20 (4) ◽

pp. 163-169

Author(s):

Joana Afonso ◽

◽

Keyword(s):

Nerve Conduction ◽

Significant Proportion ◽

Point Mutations ◽

Sensory Neuropathy ◽

Hereditary Neuropathy ◽

Pmp22 Gene ◽

Genetic Studies ◽

Molecular Features ◽

Peripheral Nerve Involvement ◽

Pressure Palsies

Introduction: Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant inherited peripheral neuropathy caused by deletions of the PMP22 gene (PMP22). It is classically characterized by episodes of repeated focal pressure neuropathies at common entrapment sites. Atypical forms are recognized and may occur in up to 56% of HNPP patients. The electrophysiological characteristics and the genetic studies are paramount for its diagnosis. We aim to describe clinical, electrophysiological and genetic features of a cohort of patients diagnosed with HNPP at a tertiary hospital. Methods: Retrospective study of patients with a confirmed diagnosis of HNPP, using descriptive statistics for their characterization. Results: Seventeen patients from 15 different families were included. Nine were males, and the overall mean age was 42.6 years-old. Age at first symptoms ranged from 3 to 46 years-old, with mean time until diagnosis of 9.3 years. Nine patients (53%) presented recurrent painless mononeuropathies or isolated focal compressive neuropathies, and eight patients (47%) had atypical presentation phenotypes, such as “Charcot-Marie-Tooth-like (CMT-like) and sensory neuropathy. Intra-familial clinical heterogeneity was observed. All patients showed nerve conduction slowing at common entrapment sites (median, ulnar and peroneal nerves), and signs of a more generalized peripheral nerve involvement were present in more than half of the patients. Fifteen patients carried the PMP22 gene deletion, and point mutations were present in two. Conclusion: Our cohort presents similar clinical characteristics to the literature description, with a significant proportion of patients with atypical presentations. The absence of clinical-electrophysiological correlation emphasise the importance of nerve conduction and genetic studies for the definite diagnosis of the disease.

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Hereditary motor and sensory neuropathy type V or complicated form of spastic paraplegia?

Klinische Neurophysiologie ◽

10.1055/s-2006-939274 ◽

2006 ◽

Vol 37 (01) ◽

Author(s):

L Schöls ◽

R Schüle ◽

B Mauko ◽

M Auer-Grumbach ◽

L Schöls

Keyword(s):

Sensory Neuropathy ◽

Spastic Paraplegia ◽

Hereditary Motor ◽

Complicated Form ◽

Type V ◽

Motor And Sensory Neuropathy

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MR imaging in hypertrophic neuropathy: A case of hereditary motor and sensory neuropathy, type i (charcot-marie-tooth)

Clinical Imaging ◽

10.1016/0899-7071(90)90073-k ◽

1990 ◽

Vol 14 (3) ◽

pp. 204-207 ◽

Cited By ~ 17

Author(s):

Samuel K. Choi ◽

Roger P. Bowers ◽

Paul E. Buckthal

Keyword(s):

Mr Imaging ◽

Sensory Neuropathy ◽

Type I ◽

Charcot Marie Tooth ◽

Hypertrophic Neuropathy ◽

Hereditary Motor ◽

Motor And Sensory Neuropathy

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Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy

npj Genomic Medicine ◽

10.1038/s41525-020-00165-6 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Hai-Lin Dong ◽

Jia-Qi Li ◽

Gong-Lu Liu ◽

Hao Yu ◽

Zhi-Ying Wu

Keyword(s):

Ex Vivo ◽

Protein Solubility ◽

Chinese Patients ◽

Hereditary Neuropathy ◽

Motor Neuropathy ◽

Causative Gene ◽

Hereditary Motor ◽

Functional Studies ◽

Hereditary Motor Neuropathy

AbstractSorbitol dehydrogenase gene (SORD) has been identified as a novel causative gene of recessive forms of hereditary neuropathy, including Charcot–Marie–Tooth disease type 2 and distal hereditary motor neuropathy (dHMN). Our findings reveal two novel variants (c.404 A > G and c.908 + 1 G > C) and one known variant (c.757delG) within SORD in four Chinese dHMN families. Ex vivo cDNA polymerase chain reaction confirmed that c.908 + 1 G > C variant was associated with impaired splicing of the SORD transcript. In vitro cell functional studies showed that c.404 A > G variant resulted in aggregate formation of SORD and low protein solubility, confirming the pathogenicity of SORD variants. We have provided more evidence to establish SORD as a causative gene for dHMN.

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