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

Sinapse ◽  
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.

scholarly journals A newly identified Thr99fsX110 mutation in the PMP22 gene associated with an atypical phenotype of the hereditary neuropathy with liability to pressure palsies.

2009 ◽  
Vol 56 (4) ◽  
Author(s):  
Izabela Moszyńska ◽  
Dagmara Kabzińska ◽  
Elena Sinkiewicz-Darol ◽  
Andrzej Kochański
Keyword(s):  
Point Mutations ◽  
Hereditary Neuropathy ◽  
Pmp22 Gene ◽  
Charcot Marie Tooth ◽  
Tooth Type ◽  
Pressure Palsies ◽  
Atypical Phenotype

Hereditary neuropathy with liability to pressure palsies (HNPP) is manifested by a spectrum of phenotypes, from the classical HNPP course associated with intermittent nerve palsies to a neuropathy resembling Charcot-Marie-Tooth type 1 (CMT1) disease. The majority of HNPP cases are associated with submicroscopical deletions in the 17p11.2-p12 region containing the PMP22 gene, while PMP22 point mutations are rare, representing about 15% of HNPP cases. In this study, we present a patient manifesting with atypical HNPP phenotype associated with a new Thr99fsX110 mutation in the PMP22 gene. We conclude that all patients who fulfill the electrophysiological criteria of HNPP, even if they lack the typical HNPP phenotype, should be tested for point mutations in the PMP22 gene.

A New Point Mutation in the PMP22 Gene in a Family Suffering From Atypical HNPP

2020 ◽  
Vol 7 (4) ◽  
pp. 505-510
Author(s):  
T. Benquey ◽  
E. Fockens ◽  
L. Kouton ◽  
E. Delmont ◽  
N. Martini ◽  
...  
Keyword(s):  
Point Mutation ◽  
Lower Limb ◽  
Autosomal Dominant ◽  
Genetic Defect ◽  
Point Mutations ◽  
Acute Onset ◽  
Hereditary Neuropathy ◽  
Pmp22 Gene ◽  
Partial Deletion ◽  
Pressure Palsies

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited disorder commonly presenting with acute-onset, non-painful focal sensory and motor mono neuropathy. In 80% of cases, the genetic defect is a 1.5 Mb deletion on chromosome 17p11.2, including PMP22. Only few cases of partial deletion and point mutations in PMP22 are involved in HNPP. We investigated a 62-years-old man with lower limb plexopathy first considered as Garland’s syndrome. A month later, his 29 years old son also consulted for paresthesia on the peroneal nerve. Targeted sequencing of the PMP22 gene identified a c.370delT (p.Trp124Glyfs*31) in both affected patients. We report a new PMP22 point mutation associated with an atypical clinical phenotype of HNPP, a painful plexopathy of the lower limb worsenen by diabetes and a mere paresthesia, but a typical ENMG. This study illustrates the large spectrum of the disease, and emphasizes the importance of a complete ENMG and family history.

scholarly journals Partial Gene Deletions ofPMP22Causing Hereditary Neuropathy with Liability to Pressure Palsies

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Sun-Mi Cho ◽  
Bo Young Hong ◽  
Yoonjung Kim ◽  
Sang Guk Lee ◽  
Jin-Young Yang ◽  
...  
Keyword(s):  
Point Mutations ◽  
Hereditary Neuropathy ◽  
Promoter Regions ◽  
Gene Deletions ◽  
Peripheral Myelin Protein 22 ◽  
Peripheral Myelin Protein ◽  
Pressure Palsies ◽  
Clinical Variation ◽  
Copy Number Changes ◽  
Dependent Probe

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal neuropathy that is commonly caused by a reciprocal 1.5 Mb deletion on chromosome 17p11.2, at the site of the peripheral myelin protein 22 (PMP22) gene. Other patients with similar phenotypes have been shown to harbor point mutations or small deletions, although there is some clinical variation across these patients. In this report, we describe a case of HNPP with copy number changes in exon or promoter regions ofPMP22. Multiplex ligation-dependent probe analysis revealed an exon 1b deletion in the patient, who had been diagnosed with HNPP in the first decade of life using molecular analysis.

Hereditary Neuropathies: Update 2017

2017 ◽  
Vol 48 (04) ◽  
pp. 282-293 ◽  
Author(s):  
Michaela Auer-Grumbach ◽  
Jan Senderek ◽  
Sabine Rudnik-Schöneborn
Keyword(s):  
Comprehensive Evaluation ◽  
Sensory Neuropathy ◽  
Classification Systems ◽  
Disease Genes ◽  
Hereditary Neuropathy ◽  
Detection Rates ◽  
Hereditary Motor ◽  
Hereditary Neuropathies ◽  
Testing Algorithms ◽  
Pressure Palsies

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.

scholarly journals Hereditary neuropathy with liability to pressure palsies in childhood: case series and update from the literature

2015 ◽  
Vol 42 (S1) ◽  
pp. S15-S15
Author(s):  
N Chrestian ◽  
C Campbell ◽  
C Poulin ◽  
H McMillan ◽  
J Vajsar
Keyword(s):  
Clinical Presentation ◽  
Case Reports ◽  
Conduction Block ◽  
Case Series ◽  
Hereditary Neuropathy ◽  
Pmp22 Gene ◽  
Gene Testing ◽  
Appropriate Care ◽  
Peroneal Palsy ◽  
Pressure Palsies

Introduction: HNPP presentation in childhood is rare and diverse and most of the published literature is based on case reports. Materials and Methods: we analyzed the data of 11 children with deletion in PMP22 gene, reviewed the published reports of HNPP in children and compared our data with the reports from the literature review. Results: Peroneal palsy was the most common presentation (50%) followed by the brachial plexus palsy in 30% of cases. The trigger of the demyelinating event was identified only in 27%. 72% of our cohort developed only one acute episode of nerve palsy. Nerve conduction studies were always suggestive of the diagnosis demonstrating 60% of cases a polyneuropathy, 50% of cases conduction block but 100% of bilateral or unilateral electrophysiologic entrapment of the median nerve at the carpal tunnel. Conclusion: The clinical presentation of HNPP in childhood is heterogeneous and EMG findings are abnormal. Any unexplained mononeuropathy or multifocal neuropathy should lead to PMP22 gene testing to look for the deletion. Early diagnosis is important for the genetic counselling but also for the appropriate care of these patients.

A frame shift mutation in the PMP22 gene in hereditary neuropathy with liability to pressure palsies

1994 ◽  
Vol 6 (3) ◽  
pp. 263-266 ◽  
Author(s):  
Garth A. Nicholson ◽  
Linda J. Valentijn ◽  
Annia K. Cherryson ◽  
Marina L. Kennerson ◽  
Tara L. Bragg ◽  
...  
Keyword(s):  
Hereditary Neuropathy ◽  
Pmp22 Gene ◽  
Frame Shift ◽  
Frame Shift Mutation ◽  
Pressure Palsies

scholarly journals Hereditary Neuropathy with Liability to Pressure Palsy Presenting with Hand Drop in a Young Child

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Inês Sobreira ◽  
Cátia Sousa ◽  
Ana Raposo ◽  
M. Rita Soares ◽  
Ana Soudo ◽  
...  
Keyword(s):  
Young Child ◽  
Male Child ◽  
Hereditary Neuropathy ◽  
Rare Entity ◽  
Genetic Studies ◽  
Left Hand ◽  
Pressure Palsy ◽  
Electrophysiological Studies ◽  
Pressure Palsies

Hereditary neuropathy with liability to pressure palsy (HNPP) results from the deletion of thePMP22gene in chromosome 17p11.2. Clinically, it presents with painless pressure palsies, typically in the 2nd and 3rd decades of life, being a rare entity in childhood. We present the case study of a six-year-old male child who presented with left hand drop that he kept for over four weeks. Electrophysiological studies suggested HNPP and genetic studies confirmed it. With this paper, we pretend to create awareness to this entity as a diagnosis to be considered in a child with painless monoparesis and to emphasize the importance of electrophysiological studies in the diagnosis.

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