hereditary neuropathies with pressure palsies

Data from gnomAD indicates that a missense mutation encoding the T118M variation in human peripheral myelin protein 22 (PMP22) is found in roughly 1 of every 75 genomes of western European lineage (1:120 in the overall human population). It is unusual among PMP22 variants that cause Charcot-Marie-Tooth disease (CMT) in that it is not 100%-penetrant. Here, we conducted cellular and biophysical studies to determine why T118M PMP22 predisposes humans to CMT, but with only incomplete penetrance. We found that T118M PMP22 is prone to mistraffic, but differs even from the WT protein in that increased expression levels do not result in a reduction in trafficking efficiency...

RATIONALE: Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominantly inherited genetic disease characterized by recurrent numbness and limb weakness. HNPP can be easily missed or misdiagnosed because of electrophysiological heterogeneity and atypical clinical symptoms. To date, diagnosis of HNPP remains a challenge for clinicians. PATIENT CONCERNS: Here, we report the case of a 12-year-old woman diagnosed with HNPP, which was initially diagnosed with Guillain-Barré Syndrome (GBS) and treated with intravenous immunoglobulin (IVIG)...

Objectives: Leigh syndrome is a progressive encephalopathy characterized by symmetrical lesions in brain. This study aimed to investigate the clinicopathologic and genetic characteristics of a family with Leigh syndrome and hereditary neuropathy with liability to pressure palsy (HNPP). Methods: Data from a Japanese family's clinical features, MRIs, muscle biopsy, and an autopsy were analyzed. A whole-exome sequence was performed, as well as real-time PCR analysis to determine copy number variations and Western blot analyses...

INTRODUCTION/AIMS: Carpal and cubital tunnel syndrome (CTS, CuTS) are common among patients with hereditary neuropathy with liability to pressure-palsies (HNPP) and Charcot-Marie-Tooth type 1A (CMT1A) and may impact quality of life. We aimed to evaluate the utility of nerve decompression surgeries in these patients. METHODS: Medical records were reviewed for patients with PMP22 mutations confirmed in Mayo Clinic laboratories from January 1999 to December 2020, who had CTS and CuTS and underwent surgical decompression...

Duplication and deletion of the peripheral myelin protein 22 ( PMP22 ) gene cause Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP), respectively, while point mutations or small insertions and deletions (indels) usually cause CMT type 1E (CMT1E) or HNPP. This study was performed to identify PMP22 mutations and to analyze the genotype-phenotype correlation in Korean CMT families. By the application of whole-exome sequencing (WES) and targeted gene panel sequencing (TS), we identified 14 pathogenic or likely pathogenic PMP22 mutations in 21 families out of 850 CMT families who were negative for 17p12 ( PMP22 ) duplication...

BACKGROUND: Limping and/or refusal to walk is a common complaint in the setting of the pediatric department, with a widely diverse differential diagnosis. An unusual etiology, is that of a hereditary neuropathy. Hereditary neuropathy with liability to pressure palsies (HNPP) is a recurrent, episodic demyelinating neuropathy, most commonly caused by a 17p11.2 chromosomal deletion encompassing the PMP22 gene. METHODS: We pursued chromosomal microarray analysis (CMA) in multiple affected individuals of a single extended family, manifesting a range of phenotypic features consistent with HNPP...

OBJECTIVE: Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsy (HNPP) are caused by mutations to the peripheral myelin protein 22 (PMP22) gene. A need exists for sensitive and reliable biomarkers of progression and treatment response. Magnetic resonance imaging (MRI) metrics of nerve pathology and morphology were investigated for this purpose. METHODS: MRI was performed at 3.0 T in the thigh of CMT1A (N = 11) and HNPP patients (N = 12) and controls (N = 23)...

INTRODUCTION: Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disorder, typically presenting with recurrent episodes of mononeuropathy in nerves susceptible to compression, with similar neurophysiological characteristics. However, other clinical and neurophysiological presentations have been reported. METHODS: We retrospectively analysed the clinical and neurophysiological characteristics of 20 patients with genetically confirmed HNPP...

Focal thickening of the myelin sheath, also known as tomacula, is a characteristic pathological feature of patients with hereditary neuropathy with liability to pressure palsies (HNPP). However, a deeper understanding of the pathology underlying unmyelinated fibers and nonmyelinating Schwann cells is required. Electron microscopic examination of sural nerve biopsy specimens was performed for 14 HNPP patients with peripheral myelin protein 22 (PMP22) deletion, and their results were compared to 12 normal controls and 14 Charcot-Marie-Tooth disease type 1A (CMT1A) patients with PMP22 duplication...

Hereditary neuropathy with liability to pressure palsy (HNPP) makes nerves increasingly susceptible to mechanical pressure at entrapment sites. Neuralgic amyotrophy (NA) can cause sudden regional weakness following events to which the patient is immunologically predisposed, such as vaccination. However, NA related to human papilloma virus (HPV) vaccination is seldom reported. We describe the case of a child with NA as the cause of a dropped shoulder following the administration of the HPV vaccine. Underlying asymptomatic HNPP was confirmed in this patient based on the electrodiagnostic findings and genetic analysis...

We present pathology of the peripheral nerves of a patient with Adult-onset Charcot-Marie-Tooth disease 4F caused by periaxin gene mutation p.D651N. The patient was a 72-year-old woman. She had hoarseness and underwent continuous positive airway pressure therapy at night due to sleep apnea. The patient died abruptly. Remarkable demyelination with tomacula formation was found in the phrenic nerve, vagal nerve, recurrent laryngeal nerve, and oculomotor nerves. The cause of death could have been insufficient reactivity to the aspiration or sudden onset of bilateral vocal cord palsy...

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...

Hereditary neuropathies are of variable genotype and phenotype. With upcoming therapies, there is urgent need for early disease recognition and outcome measures. High-resolution nerve and muscle ultrasound is a dynamic, non-invasive, well-established tool in the field of inflammatory and traumatic neuropathies. In this study, we defined nerve and muscle ultrasound parameters as recognition and progression markers in 150 patients with genetically confirmed hereditary neuropathies, including Charcot-Marie-Tooth (CMT) disease (CMT1A, n = 55; other CMT1/4, n = 28; axonal CMT, n = 15; CMTX, n = 15), hereditary neuropathy with liability to pressure palsies (HNPP, n = 16), hereditary transthyretin-amyloidosis (ATTRv, n = 14), and Fabry's disease (n = 7)...

An 18-year-old man without familial history of neuropathy developed motor and sensory disturbance of bilateral upper limbs after maintaining shoulder abduction/external rotation and elbow flection position of both upper limbs for an hour during military training. Neurological examination and electromyography studies suggested left brachial plexopathy, although a nerve conduction study (NCS) showed mild demyelination of bilateral median nerve and right ulnar nerve. Thoracic outlet syndrome (TOS) was firstly suspected because symptoms were induced by the specific position which narrows, costoclavicular and retropectoralis minor space and cause compression of the brachial plexus; however, no findings suggesting TOS were observed on computed tomography and magnetic resonance imaging...

INTRODUCTION: Point mutations in the Peripheral Myelin Protein 22 (PMP22) gene comprise less than 5% of the Charcot-Marie-Tooth (CMT) type 1 cases, and individualize either the CMT 1E subtype, or Hereditary Neuropathy with Liability to Pressure Palsy. The phenotype of CMT 1E presents with a severe early-onset polyneuropathy associated with deafness, although the clinical spectrum is broad. CASE REPORT: We describe a novel PMP22 gene point mutation (c.84G>T;p...

BackgroundCharcot-Marie-Tooth (CMT) neuropathies entail a large group of diseases with different gene mutation patterns, which produce heterogeneous phenotypes. Although health-related quality of life (HRQOL) is significantly impaired, a comprehensive assessment of HRQOL in CMT patients in Germany considering phenotypical heterogeneity represented a research gap.ObjectiveThe aim was to assess HRQOL and the satisfaction with health care in CMT patients in Germany.MethodsCMT patients >  15 years with a genetically confirmed CMT subtype were recruited through a national CMT patient registry...

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Development of peripheral nervous system (PNS) myelin involves a coordinated series of events between growing axons and the Schwann cell (SC) progenitors that will eventually ensheath them. Myelin sheaths have evolved out of necessity to maintain rapid impulse propagation while accounting for body space constraints. However, myelinating SCs perform additional critical functions that are required to preserve axonal integrity including mitigating energy consumption by establishing the nodal architecture, regulating axon caliber by organizing axonal cytoskeleton networks, providing trophic and potentially metabolic support, possibly supplying genetic translation materials and protecting axons from toxic insults...

No abstract text is available yet for this article.

AIM: To investigate the point prevalence of hereditary neuromuscular disorders on January 1, 2020 in Northern Norway. METHODS: From January 1, 1999, until January 1, 2020, we screened medical and genetic hospital records in Northern Norway for hereditary neuromuscular disorders. RESULTS: We identified 542 patients with a hereditary neuromuscular disorder living in Northern Norway, giving a point prevalence of 111.9/100,000 on January 1, 2020...