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1.
Artigo em Inglês | MEDLINE | ID: mdl-38839277

RESUMO

BACKGROUND: We aimed to investigate the clinical features of a large cohort of patients with myelin protein zero (MPZ)-related neuropathy, focusing on the five main mutation clusters across Italy. METHODS: We retrospectively gathered a minimal data set of clinical information in a series of patients with these frequent mutations recruited among Italian Charcot-Marie-Tooth (CMT) registry centres, including disease onset/severity (CMTES-CMT Examination Score), motor/sensory symptoms and use of orthotics/aids. RESULTS: We collected data from 186 patients: 60 had the p.Ser78Leu variant ('classical' CMT1B; from Eastern Sicily), 42 the p.Pro70Ser (CMT2I; mainly from Lombardy), 38 the p.Thr124Met (CMT2J; from Veneto), 25 the p.Ser44Phe (CMT2I; from Sardinia) and 21 the p.Asp104ThrfsX13 (mild CMT1B; from Apulia) mutation. Disease severity (CMTES) was higher (p<0.001) in late-onset axonal forms (p.Thr124Met=9.2±6.6; p.Ser44Phe=7.8±5.7; p.Pro70Ser=7.6±4.8) compared with p.Ser78Leu (6.1±3.5) patients. Disease progression (ΔCMTES/year) was faster in the p.Pro70Ser cohort (0.8±1.0), followed by p.Ser44Phe (0.7±0.4), p.Thr124Met (0.4±0.5) and p.Ser78Leu (0.2±0.4) patients. Disease severity (CMTES=1.2±1.5), progression (ΔCMTES/year=0.1±0.4) and motor involvement were almost negligible in p.Asp104ThrfsX13 patients, who, however, frequently (78%, p<0.001) complained of neuropathic pain. In the other four clusters, walking difficulties were reported by 69-85% of patients, while orthotic and walking aids use ranged between 40-62% and 16-28%, respectively. CONCLUSIONS: This is the largest MPZ (and late-onset CMT2) cohort ever collected, reporting clinical features and disease progression of 186 patients from five different clusters across Italy. Our findings corroborate the importance of differentiating between 'classical' childhood-onset demyelinating, late-onset axonal and mild MPZ-related neuropathy, characterised by different pathomechanisms, in view of different therapeutic targets.

2.
Eur J Neurol ; 30(8): 2461-2470, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37170966

RESUMO

BACKGROUND AND PURPOSE: Data are reported from the Italian CMT Registry. METHODS: The Italian CMT Registry is a dual registry where the patient registers and chooses a reference center where the attending clinician collects a minimal dataset of information and administers the Charcot-Marie-Tooth (CMT) Examination/Neuropathy Score. Entered data are encrypted. RESULTS: Overall, 1012 patients had registered (535 females) and 711 had received a genetic diagnosis. Demyelinating CMT (65.3%) was more common than axonal CMT2 (24.6%) and intermediate CMT (9.0%). The PMP22 duplication was the most frequent mutation (45.2%), followed by variants in GJB1 and MPZ (both ~10%) and MFN2 (3.3%) genes. A relatively high mutation rate in some "rare" genes (HSPB1 1.6%, NEFL 1.5%, SH3TC2 1.5%) and the presence of multiple mutation clusters across Italy was observed. CMT4A was the most disabling type, followed by CMT4C and CMT1E. Disease progression rate differed depending on the CMT subtype. Foot deformities and walking difficulties were the main features. Shoe inserts and orthotic aids were used by almost one-half of all patients. Scoliosis was present in 20% of patients, especially in CMT4C. Recessive forms had more frequently walking delay, walking support need and wheelchair use. Hip dysplasia occurred in early-onset CMT. CONCLUSIONS: The Italian CMT Registry has proven to be a powerful data source to collect information about epidemiology and genetic distribution, clinical features and disease progression of CMT in Italy and is a useful tool for recruiting patients in forthcoming clinical trials.


Assuntos
Doença de Charcot-Marie-Tooth , Feminino , Humanos , Doença de Charcot-Marie-Tooth/epidemiologia , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/diagnóstico , Mutação , Progressão da Doença , Itália/epidemiologia
3.
Eur J Pain ; 26(4): 929-936, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35129250

RESUMO

BACKGROUND: Pain, either nociceptive or neuropathic (NP), is a common symptom in Charcot-Marie-Tooth (CMT) disease. METHODS: We investigated small fibers involvement and its correlation with pain in different CMT subtypes through a systematic clinical and neurophysiological study. We enrolled 50 patients: 19 with duplication of PMP22 (CMT1A), 11 with mutation of MPZ (CMT1B, CMT2I/J, or CMTDID), 12 with mutation of GJB1 (CMTX1), and 8 with mutation of MFN2 (CMT2A and CMT2A2B). Pain was rated with the 11-point Numerical Rating Scale and characterized through Neuropathic Pain Symptoms Inventory. Laser-evoked potentials (LEPs) were recorded after right foot and hand stimulation and N2-P2 complex amplitude and latency were compared with those of 41 controls. RESULTS: Overall pain prevalence was 36%. NP was present in 14.6% of patients, with a length-dependent distribution in 85.7% of cases, and it was significantly more frequent in CMT1A (p < 0.001). Aδ fibers involvement greatly varies between CMT subtypes, reflecting differences in molecular pathology and pathophysiologic mechanisms. Prolonged N2 latency from foot stimulation was noted in 11 CMT1A patients, 5 of which report NP. MPZ-CMTs displayed different neurophysiological phenotypes and a very low prevalence of NP. LEPs were normal in all but one CMTX1 patients, although lower limbs N2-P2 amplitude was significantly reduced in males (p = 0.043). MFN2-CMTs were NP free and LEPs recordings were all normal. NP strictly correlated with LEPs alterations (p = 0.017). CONCLUSIONS: NP prevalence varies among CMTs subtypes and is mainly related to Aδ fibers impairment. SIGNIFICANCE: Neuropathic pain is a frequent finding in Charcot-Marie Tooth disease and is related to Aδ fibers impairment. Patients at higher risk are those belonging to certain genetic subtypes (i.e. CMT1A and CMT2J) or with laser-evoked potentials abnormalities. While managing this disease, clinicians should be aware of this symptom in order to offer best treatment options to their patients.


Assuntos
Doença de Charcot-Marie-Tooth , Potenciais Evocados por Laser , Neuralgia , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/patologia , Humanos , Masculino , Mutação , Neuralgia/epidemiologia , Neuralgia/etiologia , Fenótipo
4.
Brain Sci ; 11(12)2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34942918

RESUMO

(1) Background: Charcot-Marie-Tooth disease (CMT) is the most frequent form of inherited chronic motor and sensory polyneuropathy. Over 100 CMT causative genes have been identified. Previous reports found PMP22, GJB1, MPZ, and MFN2 as the most frequently involved genes. Other genes, such as BSCL2, MORC2, HINT1, LITAF, GARS, and autosomal dominant GDAP1 are responsible for only a minority of CMT cases. (2) Methods: we present here our records of CMT patients harboring a mutation in one of these rare genes (BSCL2, MORC2, HINT1, LITAF, GARS, autosomal dominant GDAP1). We studied 17 patients from 8 unrelated families. All subjects underwent neurologic evaluation and genetic testing by next-generation sequencing on an Ion Torrent PGM (Thermo Fischer) with a 44-gene custom panel. (3) Results: the following variants were found: BSCL2 c.263A > G p.Asn88Ser (eight subjects), MORC2 c.1503A > T p.Gln501His (one subject), HINT1 c.110G > C p.Arg37Pro (one subject), LITAF c.404C > G p.Pro135Arg (two subjects), GARS c.1660G > A p.Asp554Asn (three subjects), GDAP1 c.374G > A p.Arg125Gln (two subjects). (4) Expanding the spectrum of CMT phenotypes is of high relevance, especially for less common variants that have a higher risk of remaining undiagnosed. The necessity of reaching a genetic definition for most patients is great, potentially making them eligible for future experimentations.

5.
Neurol Sci ; 42(3): 1127-1130, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33070202

RESUMO

Charcot-Marie-Tooth disease type 1 (CMT1) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have distinct clinical and neurophysiological features that result from dysmyelination in CMT1 and macrophage-mediated segmental demyelination in CIDP. CMT1 may occur in genetically isolated cases with atypical presentations that converge phenotypically with CIDP; in rare cases, however, CMT1 may be complicated by superimposed CIDP. We report the case of a patient harboring a de novo heterozygous null mutation of the myelin protein zero (MPZ) gene and affected by subclinical CMT1B who became symptomatic due to superimposed CIDP. Peripheral nerve high-resolution ultrasound (HRUS) aided in establishing the coexistence of CMT1B and CIDP; the diagnosis was further supported by favorable clinical, neurophysiological, and ultrasound responses to immunoglobulin therapy.


Assuntos
Doença de Charcot-Marie-Tooth , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Doença de Charcot-Marie-Tooth/genética , Humanos , Proteína P0 da Mielina , Nervos Periféricos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/genética , Ultrassonografia
6.
Brain Sci ; 11(1)2020 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-33375465

RESUMO

The second most common form of Charcot-Marie-Tooth disease (CMT) follows an X-linked dominant inheritance pattern (CMTX1), referring to mutations in the gap junction protein beta 1 gene (GJB1) that affect connexin 32 protein (Cx32) and its ability to form gap junctions in the myelin sheath of peripheral nerves. Despite the advances of next-generation sequencing (NGS), attention has only recently also focused on noncoding regions. We describe two unrelated families with a c.-17+1G>T transversion in the 5' untranslated region (UTR) of GJB1 that cosegregates with typical features of CMTX1. As suggested by in silico analysis, the mutation affects the regulatory sequence that controls the proper splicing of the intron in the corresponding mRNA. The retention of the intron is also associated with reduced levels of the transcript and the loss of immunofluorescent staining for Cx32 in the nerve biopsy, thus supporting the hypothesis of mRNA instability as a pathogenic mechanism in these families. Therefore, our report corroborates the role of 5' UTR of GJB1 in the pathogenesis of CMTX1 and emphasizes the need to include this region in routine GJB1 screening, as well as in NGS panels.

7.
J Peripher Nerv Syst ; 25(4): 423-428, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33107133

RESUMO

Minifascicular neuropathy (MN) is a rare, autosomal recessive disease with prominent structural changes of peripheral nerves. So far, it has been observed in females with a 46,XY karyotype and mutations of the Desert Hedgehog (DHH) gene, thus linking MN to gonadal dysgenesis (GD) and disorders of sex development (DSD). However, a 46,XX proband with normal female sex and gender development underwent clinical evaluations, nerve conduction studies and genetic screening for a severe motor-sensory neuropathy with a pathological phenotype that hinted at MN. Indeed, sural nerve biopsy revealed a profound disturbance of perineurium development with a thin and loose structure. High-resolution ultrasound (HRUS) also disclosed diffuse changes of nerve echotexture that visibly correlated with the pathological features. After extensive genetic testing, a novel homozygous DHH null mutation (p.Ser185*) was identified in the proband and in her sister, who was affected by a similar motor-sensory neuropathy, but was eventually found to be a 46,XY patient according to a late diagnosis of DSD with complete GD. DHH should therefore be considered as a possible cause of rare non-syndromic hereditary motor-sensory neuropathies, regardless of DSD. Furthermore, HRUS could effectively smooth the complex diagnostic workup as it demonstrated a high predictive power to detect MN, providing the same detailed correlations to the pathologic features of the nerve biopsy and Dhh-/- mice in both sisters. Hence, HRUS may assume a pivotal role in guiding molecular analysis in individuals with or without DSD.


Assuntos
Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Proteínas Hedgehog/genética , Neuropatia Hereditária Motora e Sensorial , Consanguinidade , Feminino , Testes Genéticos , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Neuropatia Hereditária Motora e Sensorial/genética , Neuropatia Hereditária Motora e Sensorial/patologia , Neuropatia Hereditária Motora e Sensorial/fisiopatologia , Humanos , Microscopia Acústica , Pessoa de Meia-Idade , Irmãos , Nervo Sural/patologia , Síndrome
8.
Neuromuscul Disord ; 30(3): 227-231, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32085962

RESUMO

The Tropomyosin-receptor kinase fused gene (TFG) encodes TFG which is expressed in spinal motor neurons, dorsal root ganglia and cranial nerve nuclei, and plays a role in the dynamics of the endoplasmic reticulum. Two dominant missense TFG mutations have previously been reported in limited geographical areas (Far East, Iran, China) in association with hereditary motor sensory neuropathy with proximal involvement (HMSN-P) of the four limbs, or with Charcot-Marie-Tooth disease type 2 (CMT2). The 60-year-old female proband belonging to a three-generation Italian family presented with an atypical neuropathy characterized by diffuse painful cramps and prominent motor-sensory impairment of the distal upper limbs. Her sural nerve biopsy showed chronic axonal neuropathy without active degeneration or regeneration. Targeted next-generation sequencing of a panel with 98 genes associated with inherited peripheral neuropathies/neuromuscular disorders identified three candidate genes: TFG, DHTKD1 and DCTN2. In the family, the disease co-segregated with the TFG p.(Gly269Val) variant. TFG should be considered in genetic testing of patients with heterogeneous inherited neuropathy, independently of their ethnic origin.


Assuntos
Neuropatia Hereditária Motora e Sensorial , Proteínas/genética , Extremidade Superior/fisiopatologia , Feminino , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Neuropatia Hereditária Motora e Sensorial/genética , Neuropatia Hereditária Motora e Sensorial/patologia , Neuropatia Hereditária Motora e Sensorial/fisiopatologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Linhagem
9.
J Peripher Nerv Syst ; 25(1): 19-26, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31919945

RESUMO

Hereditary neuropathies may be misdiagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). A correct diagnosis is crucial for avoiding unnecessary therapies and access genetic counseling. We report on nine patients (seven men, mean age 49.2 ± 16.1) diagnosed with and treated as CIDP, in whom mutations or variants of unknown significance (VUS) in genes associated with hereditary neuropathies were reported. All underwent neurological and neurophysiological examination, eight also cerebrospinal fluid (CSF) analysis. In 4/9, nerve ultrasound and/or MR-neurography were performed. All the patients complained of progressive upper or lower limbs sensory-motor symptoms, with heterogeneous disease duration (1-34 years, mean 8.6 ± 10.8). Neurophysiology showed demyelinating signs in seven patients, mixed findings with predominant axonal damage in two patients. Neuroimaging disclosed diffuse abnormalities at proximal and distal segments. Molecular screening showed PMP22 duplication in two patients, mutations in the MPZ, EGR2, and GJB1 genes were reported in each of the remaining patients. The two patients with mixed neurophysiological findings had p.Val30Met mutation in the transthyretin gene. Two patients had VUS in the MARS and HSPB1 genes. Four patients had partial response to immunomodulant therapies, and CSF and neurophysiological features suggesting an inflammatory condition concomitant with the hereditary neuropathy. Hereditary neuropathy may be misdiagnosed with CIDP. The most common pitfalls are CSF (high protein levels and oligoclonal bands), incorrect interpretation of neurophysiology, and transient benefit from therapies. Neuroimaging may be helpful in cases with atypical presentations or when severe axonal damage complicate the neurophysiological interpretation.


Assuntos
Erros de Diagnóstico , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Adulto , Idoso , Feminino , Neuropatia Hereditária Motora e Sensorial/líquido cefalorraquidiano , Neuropatia Hereditária Motora e Sensorial/tratamento farmacológico , Neuropatia Hereditária Motora e Sensorial/fisiopatologia , Humanos , Fatores Imunológicos/farmacologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/líquido cefalorraquidiano , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Guias de Prática Clínica como Assunto , Ultrassonografia
10.
Neurol Sci ; 41(5): 1239-1243, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31902012

RESUMO

INTRODUCTION: Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disease. Thanks to the advances of the latest generation sequencing, more than 80 causative genes have been reported to date. METHODS: In this retrospective, observational study, we have analyzed clinical, electrophysiological, and genetic data of CMT patients in care at Neuromuscular Center of Messina University Hospital, Messina, Italy, for at least 22 years (from 1994 to 2016). Our center is the only reference center for genetic neuropathies in Sicily and in the southern part of Calabria. RESULTS: We reviewed the clinical records of 566 patients with the aim to evaluate how many patients received a genetic diagnosis and the distribution of the genetic subtypes. About 352/566 (62.19%) received a genetic diagnosis. The most frequent genetic diagnoses were CMT1A/PMP22 duplication (51.13%), followed by HNPP/PMP22 deletion (15.05%), CMT1B/MPZ mutation (10.22%), CMTX/GJB1 mutation (9.37%), and CMT2F/HSPB1 (4%). Other rare mutations included MFN2 mutation (n. 8 pts), BSCL2 mutation (n.8 pts), PMP22 point mutation (n.7 pts), GDAP1 mutation (n.4 pts), GARSmutation (n. 2 pts), TRPV4 mutation (n. 2 pts), LITAF mutation (n.1 pt), and NEFL mutation (n. 1 pt). CONCLUSIONS: Our study provides further data on frequency of CMT genes, subtypes in a wide Mediterranean area and contributes to help clinicians in addressing the genetic testing workup.


Assuntos
Doença de Charcot-Marie-Tooth/epidemiologia , Doença de Charcot-Marie-Tooth/genética , Feminino , Testes Genéticos , Humanos , Itália/epidemiologia , Masculino , Mutação , Estudos Retrospectivos , Centros de Atenção Terciária
12.
Muscle Nerve ; 60(6): 744-748, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31469427

RESUMO

INTRODUCTION: Nerve cross-sectional area (CSA) is larger than normal in Charcot-Marie-Tooth disease 1A (CMT1A), although to a variable extent. We explored whether CSA is correlated with CMT clinical severity measured with neuropathy score version 2 (CMTNS2) and its examination subscore (CMTES2) in CMT1A. METHODS: We assessed 56 patients with CMT1A (42 families). They underwent nerve conduction study (NCS) and nerve high-resolution ultrasound (HRUS) of the left median, ulnar, and fibular nerves. RESULTS: Univariate analysis showed NCS and HRUS variables to be significantly correlated with CMTNS2 and CMTES2 and with each other. Multivariate analysis showed that ulnar motor nerve conduction velocity (ß: -0.19) and fibular compound muscle action potential amplitude (-1.50) significantly influenced CMTNS2 and that median forearm CSA significantly influenced CMTNS2 (ß: 5.29) and CMTES2 (4.28). DISCUSSION: Nerve size is significantly associated with clinical scores in CMT1A, which suggests that it might represent a potential biomarker of CMT damage and progression.


Assuntos
Doença de Charcot-Marie-Tooth/fisiopatologia , Nervo Mediano/fisiopatologia , Condução Nervosa/fisiologia , Nervo Fibular/fisiopatologia , Nervo Ulnar/fisiopatologia , Adulto , Doença de Charcot-Marie-Tooth/diagnóstico por imagem , Doença de Charcot-Marie-Tooth/patologia , Feminino , Humanos , Masculino , Nervo Mediano/diagnóstico por imagem , Nervo Mediano/patologia , Pessoa de Meia-Idade , Tamanho do Órgão , Nervo Fibular/diagnóstico por imagem , Nervo Fibular/patologia , Índice de Gravidade de Doença , Nervo Ulnar/diagnóstico por imagem , Nervo Ulnar/patologia , Ultrassonografia
13.
Clin Neurophysiol ; 129(11): 2259-2267, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30216910

RESUMO

OBJECTIVE: Ulnar/median motor nerve conduction velocity (MNCV) is ≤38 m/s in demyelinating Charcot-Marie-Tooth disease (CMT). Previous nerve high resolution ultrasound (HRUS) studies explored demyelinating CMT assuming it as a homogeneous genetic/pathological entity or focused on CMT1A. METHODS: To explore the spectrum of nerve HRUS findings in demyelinating CMTs, we recruited patients with CMT1A (N = 44), CMT1B (N = 9), CMTX (N = 8) and CMT4C (N = 4). They underwent nerve conduction study (NCS) and HRUS of the median, ulnar, peroneal nerve, and the brachial plexus. RESULTS: Median, ulnar and peroneal MNCV significantly differed across CMT subtypes. Cross sectional area (CSA) was markedly and diffusely enlarged at all sites, except entrapment ones, in CMT1A, while it was slightly enlarged or within normal range in the other CMTs. No significant right-to-left difference was found. Age had limited effect on CSA. CSAs of some CMT1A patients largely overlapped with those of other demyelinating CMTs. A combination of three median CSA measures could separate CMT1A from other demyelinating CMTs. CONCLUSIONS: Nerve HRUS findings are heterogeneous in demyelinating CMTs. SIGNIFICANCE: Nerve HRUS may separate CMT1A from other demyelinating CMTs. The large demyelinating CMTs HRUS spectrum may be related to its pathophysiological variability.


Assuntos
Plexo Braquial/diagnóstico por imagem , Doença de Charcot-Marie-Tooth/diagnóstico por imagem , Ultrassonografia/métodos , Adolescente , Adulto , Idoso , Plexo Braquial/fisiopatologia , Doença de Charcot-Marie-Tooth/classificação , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Sensibilidade e Especificidade , Ultrassonografia/normas
14.
Clin Neurophysiol ; 129(1): 21-32, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29136549

RESUMO

OBJECTIVE: Nerve ultrasound (US) data on myelin protein zero (MPZ)-related Charcot-Marie-Tooth disease (CMT) are lacking. To offer a comprehensive perspective on MPZ-related CMTs, we combined nerve US with clinics, electrodiagnosis and histopathology. METHODS: We recruited 36 patients (12 MPZ mutations), and correlated nerve US to clinical, electrodiagnostic measures, and sural nerve biopsy. RESULTS: According to motor nerve conduction velocity (MNCV) criteria, nine patients were categorized as "demyelinating" CMT1B, 17 as "axonal" CMT2I/J, and 10 as dominant "intermediate" CMTDID. Sural nerve biopsy showed hypertrophic de-remyelinating neuropathy with numerous complex onion bulbs in one patient, de-remyelinating neuropathy with scanty/absent onion bulbs in three, axonal neuropathy in two, mixed demyelinating-axonal neuropathy in five. Electrodiagnosis significantly differed in CMT1B vs. CMT2I/J and CMTDID subgroups. CMT1B had slightly enlarged nerve cross sectional area (CSA) especially at proximal upper-limb (UL) sites. CSA was negatively correlated to UL MNCV and not increased at entrapment sites. Major sural nerve pathological patterns were uncorrelated to UL nerve US and MNCV. CONCLUSIONS: Sural nerve biopsy confirmed the wide pathological spectrum of MPZ-CMT. UL nerve US identified two major patterns corresponding to the CMT1B and CMT2I/J-CMTDID subgroups. SIGNIFICANCE: Nerve US phenotype of MPZ-CMT diverged from those in other demyelinating peripheral neuropathies and may have diagnostic value.


Assuntos
Doença de Charcot-Marie-Tooth/fisiopatologia , Proteína P0 da Mielina/deficiência , Adulto , Idoso , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios Motores/fisiologia , Proteína P0 da Mielina/genética , Proteína P0 da Mielina/metabolismo , Nervo Sural/diagnóstico por imagem , Nervo Sural/metabolismo , Nervo Sural/fisiopatologia , Ultrassonografia
16.
Clin Neurol Neurosurg ; 144: 67-71, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26989944

RESUMO

OBJECTIVES: CMT is a group of heterogeneous motor and sensory neuropathies divided into demyelinating (CMT1) and axonal forms (CMT2). Distal Hereditary Motor Neuropathy (dHMN) is a motor neuropathy/neuronopathy which resembles CMT. Final genetic diagnosis is poor in CMT2 and in dHMN when compared with CMT1. Our aim is to report clinical, neurophysiological and genetic findings in a cohort of patients with axonal inherited neuropathies. PATIENTS AND METHODS: We report clinical, neurophysiological and genetic findings from 45 patients with CMT2 or dHMN, coming from 39 unrelated families, observed in our Institute of Neurology over a 20-year period. RESULTS: Clinical and electrophysiological examinations showed that 38 patients had CMT2 and 7 patients presented dHMN. Extensive genetic evaluation showed 6 mutations in MFN2, 4 mutations in HSPB1, 2 mutations in BSCL2, 3 mutations in GJB1, 1 mutation in MPZ. CONCLUSION: Since next-generation sequencing will not be easily accessible, epidemiological data and clinical "phenotyping" remain the best strategy for clinicians to reach a correct genetic diagnosis in CMT2 and dHMN patients.


Assuntos
Doença de Charcot-Marie-Tooth/epidemiologia , Doença de Charcot-Marie-Tooth/genética , Neuropatia Hereditária Motora e Sensorial/epidemiologia , Neuropatia Hereditária Motora e Sensorial/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Charcot-Marie-Tooth/diagnóstico , Criança , Estudos de Coortes , Feminino , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
17.
Neurol Sci ; 36(6): 1003-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25547330

RESUMO

Mutations in the small heat-shock protein HSP27 gene are associated with distal hereditary motor neuropathy and with the axonal form of Charcot-Marie-Tooth disease type 2. We present the clinical and electrophysiological data on a multigenerational family with the p.Arg136Leu HSP27 mutation. Atypical features such as deafness and pyramidal signs were present in our cases adding new data to the large spectrum of HSP27-related phenotype.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/fisiopatologia , Proteínas de Choque Térmico HSP27/genética , Adulto , Idoso , Feminino , Proteínas de Choque Térmico , Humanos , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares , Mutação , Linhagem , Fenótipo
20.
J Peripher Nerv Syst ; 17(3): 361-4, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22971099

RESUMO

We describe the first Italian family affected by CMT2B carrying a Val162Met substitution in the RAB7 gene. The clinical and electrophysiological features of our family are similar to those of previously reported families with RAB7 mutations, also for the higher occurrence of ulcers in males. However, in this family we evaluated the autonomic nervous system, never investigated in CMT2B, by means of skin biopsy and sudomotor and cardiovascular tests. Our findings provide both pathological and functional evidence of autonomic nervous system involvement in CMT2B and expand the phenotypic characterization of CMT2B disease.


Assuntos
Doenças do Sistema Nervoso Autônomo/complicações , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doença de Charcot-Marie-Tooth/complicações , Doença de Charcot-Marie-Tooth/diagnóstico , Idoso de 80 Anos ou mais , Feminino , Humanos , Laminopatias , Masculino , Pessoa de Meia-Idade
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