6,164 results match your criteria: "Charcot-Marie-Tooth Disease"

Background: Spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot-Marie-Tooth type 2S (CMT2S) typically present before age 10. Genetic factors account for up to 50 % of neuropathies, which often display varied symptoms. Mutations in the IGHMBP2 gene are associated with both CMT2S and SMARD1, resulting in a rare clinical condition marked by axonal neuropathy, spinal muscular atrophy, respiratory distress, and muscle weakness.

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Axonal Charcot-Marie-Tooth disease (CMT2) and distal hereditary motor neuropathy (dHMN) are associated with a heterogeneous group of genes encoding proteins that are involved in axonal transport, control of RNA metabolism, mitochondrial dynamics and DNA repair. VRK1 (vaccinia-related kinase 1) is a serine/threonine kinase which is widely expressed in human tissue and plays a role in RNA maturation and processing and in DNA damage response. Variants of VRK1 have been associated with neurodevelopmental and neuromuscular disorders including pontocerebellar hypoplasia, motor neuron disorders and distal hereditary motor neuropathy.

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We report a 4.5-year-old girl with recurrent episodes of bilateral lower limb weakness following periods of upper respiratory tract infection since the age of 1.5 years.

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Mitochondrial disorders are often underrecognized as potential causes of rhabdomyolysis, a condition characterized by acute muscle breakdown that can lead to local and potentially systemic complications, with the possibility of being life-threatening. Accounts of rhabdomyolysis as a peri-operative complication associated with mitochondrial disorders are rare; therefore, this study is noteworthy. We describe a case of rhabdomyolysis that occurred during the peri-operative period in a middle-aged male with Charcot-Marie-Tooth (CMT) disease-like peripheral neuropathy.

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Exploring the phenotypic spectrum and osteopenia mechanisms in Yunis-Varón syndrome.

Genet Med Open

March 2024

Medical Genetics Division, Department of Pediatrics, CHU Sainte-Justine, Montreal, QC, Canada.

Purpose: Biallelic variants in or are associated with Yunis-Varón syndrome (YVS), which is characterized by multisystem involvement including skeletal findings, craniofacial dysmorphisms and central nervous system anomalies. Pathogenic variants in those same genes have also been associated with a predominantly neurological phenotype and with nonsyndromic conditions, such as Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis. By describing 5 new cases of -associated YVS and reviewing the literature, we better delineate the clinical phenotype associated with loss of function of those genes.

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Electrical impedance myography detects progressive pathological alterations in the hindlimb muscle of the PMP22-C3 mice, an animal model of CMT1A.

Exp Neurol

December 2024

Neuroscience Translational Medicine, Neuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. Electronic address:

Charcot-Marie-Tooth type 1A (CMT1A) is the most common inherited peripheral dysmyelinating neuropathy. Although lower limb muscle weakness is the most important factor affecting the quality of life of patients with CMT1A, existing clinical measures for its evaluation have limitations, including low sensitivity in detecting disease progression. Electrical impedance myography (EIM) is a newer tool that enables noninvasive evaluation of muscle state by measuring muscle composition, and potentially supports the evaluation of neuromuscular disease progression and treatment effects.

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Introduction: We present a case of autosomal dominant Charcot-Marie-Tooth disease type 4B3 (CMT4B3) in a family caused by a novel missense mutation.

Methods: Two patients, a mother and daughter, were recruited from our hospital. Both exhibited early-onset symptoms, including distal muscle atrophy of the limbs, without cranial nerve involvement.

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Kinesin-3 KIF1A (UNC-104 in C. elegans) is the major axonal transporter of synaptic vesicles and mutations in this molecular motor are linked to KIF1A-associated neurological disorders (KAND), encompassing Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis and hereditary spastic paraplegia. UNC-104 binds to lipid bilayers of synaptic vesicles via its C-terminal PH (pleckstrin homology) domain.

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KIF5A regulates axonal repair and time-dependent axonal transport of SFPQ granules and mitochondria in human motor neurons.

Neurobiol Dis

December 2024

Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam and VU Medical Center, Amsterdam, the Netherlands; Department of Human Genetics, Amsterdam University Medical Center, Amsterdam, the Netherlands. Electronic address:

Mutations in the microtubule-binding motor protein kinesin 5 A (KIF5A) are implicated in several adult-onset motor neuron diseases, including Amyotrophic Lateral Sclerosis, Spastic Paraplegia Type 10 and Charcot-Marie-Tooth Disease Type 2. While KIF5 family members transport a variety of cargos along axons, the specific cargos affected by KIF5A mutations remain poorly understood. Here, we generated KIF5Anull mutant human motor neurons and analyzed the impact on axonal transport and motor neuron outgrowth and regeneration in vitro.

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Connexins (Cxs) are fundamental in cell-cell communication, functioning as gap junction channels (GJCs) that facilitate solute exchange between adjacent cells and as hemichannels (HCs) that mediate solute exchange between the cytoplasm and the extracellular environment. Mutations in the GJB1 gene, which encodes Cx32, lead to X-linked Charcot-Marie-Tooth type 1 (CMTX1), a rare hereditary demyelinating disorder of the peripheral nervous system (PNS) without an effective cure or treatment. In Schwann cells, Cx32 HCs are thought to play a role in myelination by enhancing intracellular and intercellular Ca signaling, which is crucial for proper PNS myelination.

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Neurogenic disease with high CK: think muscle.

Pract Neurol

December 2024

NeuroMuscular Omnicentre (NeMO) Trento, Provincia autonoma di Trento Azienda Provinciale per i Servizi Sanitari, Trento, Italy.

Article Synopsis
  • HyperCKaemia, or elevated serum creatine kinase (CK), is frequently seen in various myopathies but can also occur in neurological disorders, making diagnosis challenging.
  • A case of a 58-year-old man illustrates the complexity, as he had a long history of muscle cramps and high CK levels, and was diagnosed with Charcot-Marie-Tooth disease type 1A through genetic testing.
  • Further genetic testing revealed a new variant related to dystrophinopathy, emphasizing the need to thoroughly investigate high CK levels in patients, even those with neurogenic disorders, to ensure proper monitoring for possible myopathy-related complications.
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How hidden is hidden hearing loss? Self-reported listening problems in charcot Marie tooth disease.

J Commun Disord

December 2024

Radboud University, Behavioural Science Institute, Nijmegen, The Netherlands. Electronic address:

Introduction: Laboratory studies have revealed hidden hearing loss in patients with Charcot-Marie-Tooth (CMT) disease, the most prevalent inherited neuropathy, which may impact their quality of life. The current study distinguished between CMT type 1, which involves demyelination of the peripheral nerves, and type 2, which concerns dysfunction of peripheral nerves due to axonopathy. The self-reported effects were investigated of CMT1 and CMT2 on listening problems and related social and attentional problems in everyday communicative situations.

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Article Synopsis
  • Genetic neuromuscular disorders significantly impact muscle function and present challenges during pregnancy, necessitating a review of related obstetric outcomes.
  • A systematic analysis of 28 studies revealed common complications such as polyhydramnios, preterm labor, and increased rates of cesarean sections among pregnant women with disorders like myotonic dystrophy and spinal muscular atrophy.
  • Effective management of these high-risk pregnancies requires collaboration between neurologists and obstetricians, alongside further research to establish standardized care protocols.
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Co-occurrence of Charcot-Marie-Tooth disease type 1 and glomerulosclerosis in a patient with a de novo INF2 variant.

BMC Nephrol

November 2024

Department of Nephrology (Key Laboratory of Management of Kidney Disease in Zhejiang Province), Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Tiyuchang Road 453, Hangzhou, 310007, People's Republic of China.

Background: Renal disease is associated with Charcot-Marie-Tooth disease (CMT), a common inherited neurological disorder. Three forms of CMT have been identified: CMT1 of the demyelinating type, CMT2 of the axonal defect type, and intermediate type (Int-CMT). INF2 is an important target for variants that cause the complex symptoms of focal segmental glomerulosclerosis (FSGS) and CMT.

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Background: Charcot-Marie-Tooth disease is a spectrum of inherited disorders characterized by both motor and sensory manifestations, which include prominent distal muscle weakness, foot deformities (pes cavus and hammer toes), and sensory deficits. Postural tremor as a manifestation of Charcot-Marie-Tooth is seldom present, except in a variant of Charcot-Marie-Tooth subtype 1 (Roussy-Levy syndrome), and its presence often results in a diagnostic dilemma.

Case Presentation: We present a 34-year-old Eritrean man who came to our hospital with a complaint of tremors of the hands of 6 months duration.

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Genetic variants in gene, encoding for the glycyl tRNA synthetase 1, cause Charcot-Marie-Tooth disease, type 2D (CMT2D). Here we describe a 14-year-old boy affected by neuropathy with prominent weakness in the upper extremities carrying two missense variants in gene: the c.803C > T, p.

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Small Complex Rearrangement in -Related Axonal Neuropathy.

Genes (Basel)

November 2024

Department of Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, Italy.

Background: Autosomal recessive inherited pathogenetic variants in the histidine triad nucleotide-binding protein 1 () gene are responsible for an axonal Charcot-Marie-Tooth neuropathy associated with neuromyotonia, a phenomenon resulting from peripheral nerve hyperexcitability that causes a spontaneous muscle activity such as persistent muscle contraction, impaired relaxation and myokymias.

Methods: Herein, we describe two brothers in whom biallelic variants were identified following a multidisciplinary approach.

Results: The younger brother came to our attention for clinical evaluation of moderate intellectual disability, language developmental delay, and some behavioral issues.

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Hereditary Neuromuscular Disorders in Reproductive Medicine.

Genes (Basel)

October 2024

Unit of Medical Genetics and Genomics, San Bortolo Hospital, ULSS n.8 "Berica", 36100 Vicenza, Italy.

Neuromuscular disorders (NMDs) encompass a broad range of hereditary and acquired conditions that affect motor units, significantly impacting patients' quality of life and reproductive health. This narrative review aims to explore in detail the reproductive challenges associated with major hereditary NMDs, including Charcot-Marie-Tooth disease (CMT), dystrophinopathies, Myotonic Dystrophy (DM), Facioscapulohumeral Muscular Dystrophy (FSHD), Spinal Muscular Atrophy (SMA), Limb-Girdle Muscular Dystrophy (LGMD), and Amyotrophic Lateral Sclerosis (ALS). Specifically, it discusses the stages of diagnosis and genetic testing, recurrence risk estimation, options for preimplantation genetic testing (PGT) and prenatal diagnosis (PND), the reciprocal influence between pregnancy and disease, potential obstetric complications, and risks to the newborn.

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Regulation of formin INF2 and its alteration in INF2-linked inherited disorders.

Cell Mol Life Sci

November 2024

Centro de Biología Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), 28049, Madrid, Spain.

Formins are proteins that catalyze the formation of linear filaments made of actin. INF2, a formin, is crucial for correct vesicular transport, microtubule stability and mitochondrial division. Its activity is regulated by a complex of cyclase-associated protein and lysine-acetylated G-actin (KAc-actin), which helps INF2 adopt an inactive conformation through the association of its N-terminal diaphanous inhibitory domain (DID) with its C-terminal diaphanous autoinhibitory domain.

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Clinical Outcome Assessments and Biomarkers in Charcot-Marie-Tooth Disease.

Neurology

December 2024

From the Department of Neurology (B.A.M.), University of Michigan Medical School, Ann Arbor; and Department of Neurology (V.F.), University of Colorado Anschutz Medical Campus, Aurora.

Charcot-Marie-Tooth disease (CMT) encompasses a diverse group of genetic forms of inherited peripheral neuropathy and stands as the most common hereditary neurologic disease worldwide. At present, no disease-modifying treatments exist for any form of CMT. However, promising therapeutic strategies are rapidly emerging, necessitating careful consideration of clinical outcome assessments (COAs) and clinical trial design.

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Article Synopsis
  • * Researchers analyzed data from 275 CMTX1 patients across 13 centers in France, finding that those with mutations in transmembrane domains had more severe symptoms and earlier onset than those with mutations in intracellular or extracellular domains.
  • * The findings suggest that the type of genetic mutation not only helps diagnose CMTX1 but also predicts disease severity, emphasizing the need to consider these correlations in upcoming clinical research.
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Autoantibodies Against Dihydrolipoamide S-Acetyltransferase Are Not Associated With Immune-Mediated Neuropathies.

Neurol Neuroimmunol Neuroinflamm

January 2025

From the Department of Immunology (A.J.), CHU Montpellier; Institut de Génomique Fonctionnelle (A.J., J.E.-B., G.T., J.D.), Université de Montpellier, CNRS, INSERM; and Department of Neurology (G.T.), CHU Montpellier, France.

Objectives: Dihydrolipoamide S-acetyltransferase (DLAT), the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC-E2), has recently been suggested to be a biomarker of chronic inflammatory demyelinating polyneuropathy (CIDP). It was particularly associated with sensory variants of CIDP. Antimitochondrial antibodies are important for the diagnosis of primary biliary cholangitis, but insofar, only 2 studies have reported an association with CIDP.

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Background: Targeted next generation sequence analyses in a cohort of 961 previously described patients with clinically suspected Duchene muscular dystrophy (DMD) revealed that 145/961 (15%) had variants in genes associated with other muscular dystrophies (OMDs).

Methods: NGS was carried out in DMD negative patients after deletion/duplication analysis followed by WES for No variant cases.

Results: The majority of patients with OMDs had autosomal recessive diseases that included Limb-Girdle Muscular Dystrophies (LGMDs), Bethlem, Ullrich congenital Myopathies and Emery-Driefuss muscular dystrophy.

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