1,920 results match your criteria: "Facioscapulohumeral Dystrophy"

Longitudinal Insights Into Childhood Onset Facioscapulohumeral Dystrophy: A 5-Year Natural History Study.

Neurology

January 2025

From the Department of Neurology (J.N.D., H.T.M.B., N.V.A., B.G.M.V.E., N.C.V.); Department of Pediatric Neurology (J.N.D., H.T.M.B., A.K., C.E.E.), Donders Institute for Brain, Cognition and Behaviour, Amalia Children's Hospital, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Neurology (R.J.M.G.), Jönköping, and Department of Biomedical and Clinical Sciences, Linköping University, Sweden; Department of Rehabilitation (M.M.P., S.L.S.H.), Donders Institute for Brain, Cognition and Behaviour, Amalia Children's Hospital; and Department of Neurology (N.V.A.), Clinical Neuromuscular Imaging Group, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.

Background And Objectives: Facioscapulohumeral dystrophy (FSHD) is an inherited muscle disorder, with childhood onset in 20% of patients. Understanding the natural history of childhood FSHD and identifying clinical and functional outcome measures are crucial for clinical care and future trials.

Methods: In a prospective nationwide FSHD cohort study (iFocus), 20 childhood-onset patients were assessed at baseline, 2 years, and 5 years.

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Article Synopsis
  • - The study focuses on Facioscapulohumeral dystrophy type 1 (FSHD1), a serious muscle disorder, and emphasizes the need for a comprehensive approach to understand its genetics.
  • - Researchers conducted genome sequencing and linkage analysis in a family suspected of having FSHD1, identifying a specific disease locus on chromosome 4q35.2.
  • - By using advanced ultra-long-read genome sequencing, they successfully genotyped a pathogenic allele associated with FSHD1, highlighting the effectiveness of these genomic tools in disease mapping and characterization.
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Objective: Reliable, circulating biomarkers for Duchenne, Becker and facioscapulohumeral muscular dystrophies (DBMD and FSHD) remain unvalidated. Here, we investigated the plasma extracellular vesicle (EV) proteome to identify disease-specific biomarkers that could accelerate therapy approvals.

Methods: We extracted EVs from the plasma of DBMD and FSHD patients and healthy controls using size-exclusion chromatography, conducted mass spectrometry on the extracted EV proteins, and performed comparative analysis to identify disease-specific biomarkers.

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Article Synopsis
  • FSHD is a muscle-wasting disease caused by the misexpression of the DUX4 transcription factor, leading to progressive muscle weakness starting from facial and shoulder muscles and eventually affecting the lower limbs.
  • The study utilized siRNAs to investigate the role of SIX family transcription factors in regulating DUX4 expression in patient-derived FSHD muscle cells, revealing that SIX1, SIX2, and SIX4 are essential for DUX4 induction during muscle differentiation.
  • Additionally, the research indicated that DUX4 actually downregulates SIX RNA levels, suggesting a negative feedback loop in the regulation of these transcription factors in FSHD contexts.
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Germline mutations in SMCHD1, DNMT3B and LRIF1 can cause facioscapulohumeral muscular dystrophy type 2 (FSHD2). FSHD is an epigenetic skeletal muscle disorder in which partial failure in heterochromatinization of the D4Z4 macrosatellite repeat causes spurious expression of the repeat-embedded gene in skeletal muscle, ultimately leading to muscle weakness and wasting. All three proteins play a role in chromatin organization and gene silencing; however, their functional relationship has not been fully elucidated.

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Optical genome mapping reveals maternal mosaicism in two Sibling cases of Early-Onset Facioscapulohumeral muscular dystrophy type 1.

Clin Chim Acta

January 2025

Neonatology Department, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China; Shandong Provincial Clinical Research Center for Children's Health and Disease, Jinan, China. Electronic address:

Background: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant condition caused by shortened D4Z4 repeat units in the subtelomeric region of 4q35, always on the 4qA haplotype, or due to variants in the SMCHD1 gene leading to hypomethylation of the D4Z4 macrosatellite DNA repeats.

Methods: To explore the potential genetic basis for suspected FSHD presenting with early onset in two siblings without evident family history of the disorder, whole genome sequencing (WGS) and optical genome mapping (OGM) were conducted on the affected individuals and their parents.

Results: The two siblings manifested severe and early-onset clinical features consistent with FSHD, initiating with facial muscle weakness that progressively spread downward since the age of four months.

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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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Facioscapulohumeral muscular dystrophy (FSHD) is caused by the epigenetic de-repression of the double homeobox 4 (DUX4) gene, leading to asymmetric muscle weakness and atrophy that begins in the facial and scapular muscles and progresses to the lower limbs. This incurable condition can severely impair muscle function, ultimately resulting in a loss of ambulation. A thorough analysis of molecular factors associated with the varying degrees of muscle impairment in FSHD is still lacking.

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Respiratory function and evaluation in individuals with facioscapulohumeral muscular dystrophy in the Muscular Dystrophy Surveillance, Tracking and Research Network.

Neuromuscul Disord

November 2024

Department of Epidemiology, College of Public Health, University of Iowa, S416 CPHB, 145 N Riverside Dr, Iowa City, Iowa 52242, United States. Electronic address:

Article Synopsis
  • A study using data from the MD STARnet examined respiratory testing and insufficiency in people with facioscapulohumeral muscular dystrophy (FSHD) diagnosed between 2008-2016.
  • Out of 170 individuals with FSHD, only 20% received pulmonary function tests, and 14.1% had polysomnograms; however, over half of those tested showed significant respiratory issues.
  • The findings suggest a need for better monitoring and adherence to guidelines recommending that all FSHD patients receive baseline respiratory evaluations to identify complications early.
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Background: Facioscapulohumeral Muscular Dystrophy (FSHD) is a genetically linked disorder characterized by the progressive deterioration of muscles controlling facial and scapular movement. The severity and distribution of affected muscle groups vary significantly across patient demographics, necessitating diverse assistive approaches.

Objective: This review aims to evaluate the effectiveness of assistive devices and therapeutic options, including medications and rehabilitative therapies, tailored to specific manifestations of FSHD.

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Facioscapulohumeral muscular dystrophy (FSHD) is caused by sporadic misexpression of the transcription factor double homeobox 4 (DUX4) in skeletal muscles. So far, monolayer cultures and animal models have been used to study the FSHD disease mechanism and for FSHD therapy development, but these models do not fully recapitulate the disease and there is a lack of knowledge on how DUX4 misexpression leads to skeletal muscle dysfunction. To overcome these barriers, we have developed a three-dimensional tissue engineered skeletal muscle (3D-TESM) model by generating genetically matched myogenic progenitors (MPs) from human induced pluripotent stem cells of three mosaic FSHD patients.

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Introduction/aims: The number of clinical trials in facioscapulohumeral muscular dystrophy (FSHD) is expected to increase in the near future. There is a need for clinical outcome assessments (COAs) that can capture disease progression over the relatively short time span of a clinical trial. In this study, we report the natural progression of FSHD and determine the feasibility of COAs for clinical trials.

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Muscular dystrophy encompasses a group of genetic conditions with progressive muscle damage and weakness. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders that affect the production of the protein dystrophin. Emery-Dreifuss muscular dystrophy (EDMD) is typically an X-linked-recessive disorder involving the gene that codes for emerin.

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Temporal variation in p38-mediated regulation of DUX4 in facioscapulohumeral muscular dystrophy.

Sci Rep

November 2024

Deparment of Biochemistry and Molecular Biology, Saint Louis University, Doisy Research #4171100 South Grand, Saint Louis, MO, 63104, USA.

Facioscapulohumeral muscular dystrophy (FSHD) is a degenerative muscle disease caused by loss of epigenetic silencing and ectopic reactivation of the embryonic double homeobox protein 4 gene (DUX4) in skeletal muscle. The p38 MAP kinase inhibitor losmapimod is currently being tested in FSHD clinical trials due to the finding that p38 inhibition suppresses DUX4 expression in preclinical models. However, the role of p38 in regulating DUX4 at different myogenic stages has not been investigated.

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Background: Facioscapulohumeral muscular dystrophy 1 (FSHD1) is an autosomal dominant muscular disorder mainly caused by the contraction and hypomethylation of the D4Z4 repeat array in chromosome 4q35. Prenatal diagnosis of FSHD1 is challenging due to the highly repetitive and long genomic structure. In this study, a pregnant woman diagnosed with FSHD1 using optical genome mapping sought assistance for a healthy offspring.

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Deciphering the Complexity of FSHD: A Multimodal Approach as a Model for Rare Disorders.

Int J Mol Sci

October 2024

Genomic Medicine Laboratory UILDM, IRCCS Fondazione Santa Lucia, Via Ardeatina 306-354, 00179 Rome, Italy.

Rare diseases are heterogeneous diseases characterized by various symptoms and signs. Due to the low prevalence of such conditions (less than 1 in 2000 people), medical expertise is limited, knowledge is poor and patients' care provided by medical centers is inadequate. An accurate diagnosis is frequently challenging and ongoing research is also insufficient, thus complicating the understanding of the natural progression of the rarest disorders.

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Background: Facioscapulohumeral dystrophy (FSHD) is a myopathy characterized by the loss of repressive epigenetic features affecting the D4Z4 locus (4q35). The assessment of DNA methylation at two regions (DUX4-PAS and DR1) of D4Z4 locus proved to be an effective method to detect epigenetic signatures compatible with FSHD. The present study aims at validating the employment of this method into clinical practice and improving the protocol by refining the classification thresholds of 4qA/4qA patients.

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Genomic repeat sequences are patterns of nucleic acids that exist in multiple copies throughout the genome. More than 60 Mendelian disorders are caused by the expansion or contraction of these repeats. Various specific methods for determining tandem repeat variations have been developed.

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Muscular dystrophy as a cause of unilateral scapular winging.

Intern Med J

October 2024

Department of Neurology and Clinical Neurophysiology, Royal North Shore Hospital, Sydney, New South Wales, Australia.

Shoulder weakness with unilateral scapular winging is a common issue that initially presents to the general physician, sports physician or rheumatologist. Although most of these cases are neurogenic in nature, it is important to consider alternative causes for unilateral scapular winging. Muscular dystrophies can present with marked asymmetry, the most typical being facioscapulohumeral dystrophy (FSHD).

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Article Synopsis
  • Facioscapulohumeral muscular dystrophy (FSHD) is a rare muscular dystrophy that increases the risk of serious complications during surgery, such as hyperkalemia and rhabdomyolysis.
  • This case report focuses on the anesthetic management of a child with FSHD who underwent an exploratory tympanotomy, highlighting the challenges involved due to the condition.
  • Notably, this is the first documented instance of pediatric general anesthesia for a patient with FSHD that also involved the use of sugammadex for reversing neuromuscular blockade.
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The term "dyskinesia" has often been used interchangeably with "winging," leading to ambiguity in the literature. To address this, the broader term "scapulothoracic abnormal motion (STAM)" was introduced to describe any abnormal position or movement of the scapula on the chest, resulting in pain and dysfunction. Scapulothoracic abnormal motion has a wide range of causes, including musculoskeletal imbalances such as pectoralis minor hyperactivity, neurological impairments such as long thoracic nerve palsy, and genetic conditions like facioscapulohumeral muscular dystrophy (FSHD).

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The other face of facioscapulohumeral muscular dystrophy: Exploring orofacial weakness using muscle ultrasound.

Muscle Nerve

November 2024

Department of Neurology, Clinical Neuromuscular Imaging Group, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.

Introduction/aims: One of the most distinct clinical features of facioscapulohumeral muscular dystrophy (FSHD) is facial weakness. It leads to diminished facial expression and functional impairments. Despite its clinical relevance, little else is known about orofacial muscle involvement.

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Expression of the double homeobox 4 () transcription factor is highly regulated in early embryogenesis and is subsequently epigenetically silenced. Ectopic expression of due to hypomethylation of the D4Z4 repeat array on permissive chromosome 4q35 alleles is associated with facioscapulohumeral muscular dystrophy (FSHD). In peripheral blood samples from 188 healthy individuals, D4Z4 methylation was highly variable, ranging from 19% to 76%, and was not affected by age.

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