910 results match your criteria American Journal Of Medical Genetics Part C-Seminars In Medical Genetics[Journal]


Biallelic variants in CENPF causing a phenotype distinct from Strømme syndrome.

Am J Med Genet C Semin Med Genet 2022 Mar 30;190(1):102-108. Epub 2022 Apr 30.

Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy.

Biallelic loss-of-function (LoF) variants in CENPF gene are responsible for Strømme syndrome, a condition presenting with intestinal atresia, anterior ocular chamber anomalies, and microcephaly. Through an international collaboration, four individuals (three males and one female) carrying CENPF biallelic variants, including two missense variants in homozygous state and four LoF variants, were identified by exome sequencing. All individuals had variable degree of developmental delay/intellectual disability and microcephaly (ranging from -2. Read More

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The role of cilia for hydrocephalus formation.

Am J Med Genet C Semin Med Genet 2022 Mar 26;190(1):47-56. Epub 2022 Apr 26.

Department of General Pediatrics, University Clinic Muenster, Münster, Germany.

Hydrocephalus is a common finding in newborns. In most cases, it is caused by intraventricular hemorrhage associated with prematurity, whereas in some patients the cause of hydrocephalus can be traced back to genetic changes, associated with disease syndromes such as RASopathies, lysosomal storage diseases, dystroglycanopathies, craniosynostosis but also ciliopathies. Ciliopathies are a group of diseases that can affect multiple organ systems due to dysfunction or the absence of cilia. Read More

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Role of primary cilia and Hedgehog signaling in craniofacial features of Ellis-van Creveld syndrome.

Am J Med Genet C Semin Med Genet 2022 Mar 8;190(1):36-46. Epub 2022 Apr 8.

The Ohio State University College of Dentistry, Columbus, Ohio, USA.

Ellis-van Creveld syndrome (EvC) is an autosomal recessive genetic disorder involving pathogenic variants of EVC and EVC2 genes and classified as a ciliopathy. The syndrome is caused by mutations in the EVC gene on chromosome 4p16, and EVC2 gene, located close to the EVC gene, in a head-to-head configuration. Regardless of the affliction of EVC or EVC2, the clinical features of Ellis-van Creveld syndrome are similar. Read More

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Bardet-Biedl syndrome: The pleiotropic role of the chaperonin-like BBS6, 10, and 12 proteins.

Am J Med Genet C Semin Med Genet 2022 Mar 4;190(1):9-19. Epub 2022 Apr 4.

Unit of Nephrology, Department of Translational Medical Sciences, University of Campania L. Vanvitelli, Naples, Italy.

Bardet-Biedl syndrome (BBS) is a rare pleiotropic disorder known as a ciliopathy. Despite significant genetic heterogeneity, BBS1 and BBS10 are responsible for major diagnosis in western countries. It is well established that eight BBS proteins, namely BBS1, 2, 4, 5, 7, 8, 9, and 18, form the BBSome, a multiprotein complex serving as a regulator of ciliary membrane protein composition. Read More

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Chronic airway disease in primary ciliary dyskinesia-spiced with geno-phenotype associations.

Am J Med Genet C Semin Med Genet 2022 Mar 29;190(1):20-35. Epub 2022 Mar 29.

Department of Paediatrics and Adolescent Medicine, Danish PCD & chILD Centre, CF Centre Copenhagen, Paediatric Pulmonary Service, ERN Accredited, Copenhagen, Denmark.

Primary ciliary dyskinesia (PCD) can be defined as a multiorgan ciliopathy with a dominant element of chronic airway disease affecting the nose, sinuses, middle ear, and in particular, the lower airways. Although most patients with PCD are diagnosed during preschool years, it is obvious that the chronic lung disease starts its course already from birth. The many faces of the clinical picture change, as does lung function, structural lung damage, the burden of infection, and of treatment throughout life. Read More

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Primary ciliary dyskinesia in Volendam: Diagnostic and phenotypic features in patients with a CCDC114 mutation.

Am J Med Genet C Semin Med Genet 2022 Mar 27;190(1):89-101. Epub 2022 Mar 27.

Department of Pediatric Respiratory Medicine and Allergy, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

Primary ciliary dyskinesia (PCD) is a heterogeneous disease, with impaired mucociliary clearance causing respiratory tract infections. A founding CCDC114 mutation has led to a relatively homogeneous and large Dutch PCD population in Volendam. Our aim was to describe their phenotype. Read More

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Systematic analysis of physical examination characteristics of 94 individuals with Joubert syndrome: Keys to suspecting the diagnosis.

Am J Med Genet C Semin Med Genet 2022 Mar 21;190(1):121-130. Epub 2022 Mar 21.

Department of Pediatrics and McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Joubert syndrome (JS) is a neurodevelopmental disorder characterized by hypotonia and developmental delay, as well as the obligatory molar tooth sign on brain imaging. Since hypotonia and developmental delay are nonspecific features, there must be a high level of clinical suspicion of JS so that the diagnostic brain imaging and/or molecular testing for the >38 genes associated with JS is/are obtained. The goal of this study was to analyze clinical photographs of a cohort of patients with JS to define a list of physical examination features that should prompt investigation for JS. Read More

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Unlocking the potential of the UK 100,000 Genomes Project-lessons learned from analysis of the "Congenital Malformations caused by Ciliopathies" cohort.

Am J Med Genet C Semin Med Genet 2022 Mar 15;190(1):5-8. Epub 2022 Mar 15.

Division of Molecular Medicine, Leeds Institute of Medical Research at St. James's, University of Leeds, St. James's University Hospital, Leeds, UK.

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Biallelic variants in TTC21B as a rare cause of early-onset arterial hypertension and tubuloglomerular kidney disease.

Am J Med Genet C Semin Med Genet 2022 Mar 15;190(1):109-120. Epub 2022 Mar 15.

Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

Monogenic disorders of the kidney typically affect either the glomerular or tubulointerstitial compartment producing a distinct set of clinical phenotypes. Primary focal segmental glomerulosclerosis (FSGS), for instance, is characterized by glomerular scarring with proteinuria and hypertension while nephronophthisis (NPHP) is associated with interstitial fibrosis and tubular atrophy, salt wasting, and low- to normal blood pressure. For both diseases, an expanding number of non-overlapping genes with roles in glomerular filtration or primary cilium homeostasis, respectively, have been identified. Read More

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Genotype-phenotype correlates in Joubert syndrome: A review.

Am J Med Genet C Semin Med Genet 2022 Mar 3;190(1):72-88. Epub 2022 Mar 3.

Neurogenetics Research Center, IRCCS Mondino Foundation, Pavia, Italy.

Joubert syndrome (JS) is a genetically heterogeneous primary ciliopathy characterized by a pathognomonic cerebellar and brainstem malformation, the "molar tooth sign," and variable organ involvement. Over 40 causative genes have been identified to date, explaining up to 94% of cases. To date, gene-phenotype correlates have been delineated only for a handful of genes, directly translating into improved counseling and clinical care. Read More

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OFD1: One gene, several disorders.

Am J Med Genet C Semin Med Genet 2022 Mar 2;190(1):57-71. Epub 2022 Feb 2.

Scuola Superiore Meridionale, Naples, Italy.

The OFD1 protein is necessary for the formation of primary cilia and left-right asymmetry establishment but additional functions have also been ascribed to this multitask protein. When mutated, this protein results in a variety of phenotypes ranging from multiorgan involvement, such as OFD type I (OFDI) and Joubert syndromes (JBS10), and Primary ciliary dyskinesia (PCD), to the engagement of single tissues such as in the case of retinitis pigmentosa (RP23). The inheritance pattern of these condition differs from X-linked dominant male-lethal (OFDI) to X-linked recessive (JBS10, PCD, and RP23). Read More

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Parental perceptions of bladder dysfunction in children with symptomatic joint hypermobility.

Am J Med Genet C Semin Med Genet 2021 12 29;187(4):586-592. Epub 2021 Nov 29.

UCL Great Ormond Street Institute of Child Health, University College London, London, UK.

Children with symptomatic joint hypermobility (SJH) report chronic pain, fatigue, and joint instability as their main symptoms. Symptoms can extend beyond musculoskeletal and include lower urinary tract dysfunction (LUTD). There are no studies exploring parent-perceived quality of life (QoL) in children with LUTD, or strategies used to manage symptoms in this population. Read More

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December 2021

Orthopedic considerations and surgical outcomes in Ehlers-Danlos syndromes.

Am J Med Genet C Semin Med Genet 2021 12 29;187(4):458-465. Epub 2021 Nov 29.

Kathryn O. and Alan C. Greenberg Center for Skeletal Dysplasias, Hospital for Special Surgery, New York, New York, USA.

The Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of connective tissue disorders with varying physical manifestations. There are no clear guidelines for addressing orthopedic concerns or reporting surgical outcomes in this population. This article reviews the literature, reports on a new study, and offers considerations prior to surgical intervention. Read More

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December 2021

Initial description and evaluation of EDS ECHO: An international effort to improve care for people with the Ehlers-Danlos syndromes and hypermobility spectrum disorders.

Am J Med Genet C Semin Med Genet 2021 12 25;187(4):609-615. Epub 2021 Nov 25.

The Ehlers-Danlos Society, New York, USA and London, UK.

The Ehlers-Danlos Society Extension for Community Health Care Outcomes (EDS ECHO) is a portfolio of teleconferencing programs developed around the principles and practices of Project ECHO®, aimed at increasing awareness of Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD) among clinicians, enhancing their confidence in the assessment and management of these complex conditions, and generating networks of clinicians across specialties. We assessed the outcomes of the first EDS ECHO program, launched in April 2019, with two hub locations: Indiana University Health, Indianapolis, Indiana, USA, and The Royal Society of Medicine, London, UK. Clinicians were surveyed before and 6 months after their participation. Read More

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December 2021

Respiratory manifestations in the Ehlers-Danlos syndromes.

Am J Med Genet C Semin Med Genet 2021 12 22;187(4):533-548. Epub 2021 Nov 22.

Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Persons with the Ehlers-Danlos syndromes (EDS) report a wide range of respiratory symptoms, most commonly shortness of breath, exercise limitation, and cough. Also reported are noisy breathing attributed to asthma, difficulty with deep inhalation, and inspiratory thoracic pain. The literature consists of case reports and small cross-sectional and cohort studies. Read More

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December 2021

Updates on the psychological and psychiatric aspects of the Ehlers-Danlos syndromes and hypermobility spectrum disorders.

Am J Med Genet C Semin Med Genet 2021 12 22;187(4):482-490. Epub 2021 Nov 22.

Institut Neuropsychiatry and Addictions, Parc Salut Mar, Hospital del Mar, Barcelona, Spain.

The field of the psychiatric and psychological aspects of Ehlers-Danlos syndromes (EDS) has been understudied and neglected for many years. People with EDS are often classified as "somatizers" by untrained clinicians. However, research on the biological basis of EDS is improving our understanding of the physiology and psychopathology of the disorder. Read More

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December 2021

Variant connective tissue (joint hypermobility) and dysautonomia are associated with multimorbidity at the intersection between physical and psychological health.

Am J Med Genet C Semin Med Genet 2021 12 22;187(4):500-509. Epub 2021 Nov 22.

Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Falmer, UK.

The symptoms of joint hypermobility extend beyond articular pain. Hypermobile people commonly experience autonomic symptoms (dysautonomia), and anxiety or related psychological issues. We tested whether dysautonomia might mediate the association between hypermobility and anxiety in adults diagnosed with mental health disorders and/or neurodevelopmental conditions (hereon referred to as patients), by quantifying joint hypermobility and symptoms of autonomic dysfunction. Read More

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December 2021

Throat and voice problems in Ehlers-Danlos syndromes and hypermobility spectrum disorders.

Am J Med Genet C Semin Med Genet 2021 12 20;187(4):527-532. Epub 2021 Nov 20.

Department of Otolaryngology, Royal National ENT and Eastman Dental Hospitals, University College Hospitals NHS Foundation Trust and University College London, London, UK.

A small number of case reports and observational studies describe chronic nasal congestion, upper airway obstruction, dysphonia, vocal cord abnormalities, and swallowing abnormalities in the Ehlers-Danlos syndromes. Little is known of the causes and therefore treatments of these, yet they are not uncommon findings in persons with hypermobility-related conditions presenting in the healthcare setting. We have a specialist multidisciplinary ear, nose, and throat and speech therapy practice with accumulating observational and empirical experience of managing these conditions, which include altered voice, choking, high dysphagia and anterior and deep neck pains. Read More

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December 2021

Urogynaecology and Ehlers-Danlos syndrome.

Am J Med Genet C Semin Med Genet 2021 12 20;187(4):579-585. Epub 2021 Nov 20.

Department of Urogynaecology, St. Mary's Hospital, Imperial College Healthcare NHS Trust, Paddington, London, UK.

Ehlers-Danlos syndrome (EDS) can lead to a presentation to urogynaecology services with multiple symptoms including vaginal prolapse, overactive bladder symptoms, voiding dysfunction, bladder pain syndrome, recurrent urinary tracts infections, stress urinary incontinence, recurring bladder diverticula, vesicoureteral reflux, pelvic floor pain or spasms, and complicated postnatal perineal wounds. This article explores the pathophysiology of these conditions in causing urinary urgency, incontinence, and infections; highlighting the key investigations and management considerations for women with EDS including conservative, pharmacological, and surgical. Read More

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December 2021

Pain in the Ehlers-Danlos syndromes: Mechanisms, models, and challenges.

Am J Med Genet C Semin Med Genet 2021 12 19;187(4):429-445. Epub 2021 Nov 19.

Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.

Chronic pain is one of the most common, yet poorly studied, complaints in people suffering from Ehlers-Danlos syndromes (EDS). This heterogeneous group of heritable connective tissue disorders is typically characterized by skin hyperextensibility, joint hypermobility, and generalized connective tissue fragility. Most EDS types are caused by genetic defects that affect connective tissue biosynthesis, thereby compromising collagen biosynthesis or fibrillogenesis and resulting in a disorganized extracellular matrix. Read More

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December 2021

Ehlers-Danlos syndromes, hypermobility spectrum disorders, and associated co-morbidities: Reports from EDS ECHO.

Am J Med Genet C Semin Med Genet 2021 12 18;187(4):413-415. Epub 2021 Nov 18.

Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.

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December 2021

Obstetrics and gynecology in Ehlers-Danlos syndrome: A brief review and update.

Am J Med Genet C Semin Med Genet 2021 12 12;187(4):593-598. Epub 2021 Nov 12.

Harvey Institute for Human Genetics, Greater Baltimore Medical Center, Baltimore, Maryland, USA.

The Ehlers-Danlos syndromes (EDSs) are a group of hereditary disorders affecting collagen and connective tissue. Gynecologic and obstetric complications occur with increased frequency and severity due to these abnormalities. Recent studies suggest that some complications, including endometriosis and premature rupture of the membranes may occur less often than previously thought. Read More

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December 2021

Dysautonomia in the Ehlers-Danlos syndromes and hypermobility spectrum disorders-With a focus on the postural tachycardia syndrome.

Am J Med Genet C Semin Med Genet 2021 12 12;187(4):510-519. Epub 2021 Nov 12.

The Wellington Hospital, London, UK.

Dysautonomia (autonomic dysfunction) occurs in the Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD). Symptoms include palpitations, dizziness, presyncope, and syncope, especially when standing upright. Symptoms of orthostatic intolerance are usually relieved by sitting or lying and may be exacerbated by stimuli in daily life that cause vasodilatation, such as food ingestion, exertion, and heat. Read More

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December 2021

A case-control study of respiratory medication and co-occurring gastrointestinal prescription burden among persons with Ehlers-Danlos syndromes.

Am J Med Genet C Semin Med Genet 2021 12 12;187(4):549-560. Epub 2021 Nov 12.

Department of Public Health Sciences, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.

We previously reported increased pain and gastrointestinal (GI) medication prescription claims among persons with Ehlers-Danlos syndromes (EDS) and peripubertal increase in opioid and anti-emetic claims among women with EDS. Herein, we hypothesized a higher proportion of respiratory and co-occurring respiratory and GI medication prescription claims among persons with EDS compared to their matched controls with increases among peripubertal women with EDS. We compared the proportions of respiratory and co-occurring respiratory and GI medication prescription claims among persons with EDS (aged 5-62) against their age-, sex-, state of residence-, and earliest claim date-matched controls using 10 years of private prescription claims data. Read More

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December 2021

Surgical treatment of abdominal compression syndromes: The significance of hypermobility-related disorders.

Am J Med Genet C Semin Med Genet 2021 12 7;187(4):570-578. Epub 2021 Nov 7.

EVK Mettmann, Academic Teaching Hospital, University of Duisburg-Essen, Mettmann, NRW, Germany.

Case reports and systematic studies of the most common hypermobility-related disorders, hypermobile Ehlers-Danlos syndrome (hEDS), and hypermobility spectrum disorder (HSD) typically describe gastroenterological symptoms and complaints attributed to structural malfunction, autonomic dysfunction, or inflammation of the gastrointestinal tract. However, abdominal compression syndromes (CS) may also contribute to pain and dysfunction in these individuals and be the leading pathology given symptoms significantly reduce or cease after decompressive surgery. Arising not only in the abdomen and causing pain (median arcuate ligament syndrome [MALS] and superior mesenteric artery syndrome [SMAS]), CS also occur in the retroperitoneum and the pelvis (nutcracker syndrome and May-Thurner syndrome), these latter conditions causing chronic pelvic congestion syndrome (PCS). Read More

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December 2021

High rate of dyspareunia and probable vulvodynia in Ehlers-Danlos syndromes and hypermobility spectrum disorders: An online survey.

Am J Med Genet C Semin Med Genet 2021 12 7;187(4):599-608. Epub 2021 Nov 7.

Department of Human Development Nursing Science, College of Nursing, University of Illinois Chicago, Chicago, Illinois, USA.

Vulvodynia is debilitating vulvar pain accompanied by dyspareunia (pain with sexual intercourse). Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD) may represent a predisposing factor for vulvodynia given a high rate of dyspareunia in these conditions. We conducted an online survey of women with EDS or HSD to assess rates of dyspareunia and estimate rates of vulvodynia, report rates of comorbid conditions common to EDS or HSD and vulvodynia, and examine rates of conditions contributing to dyspareunia in women with EDS or HSD. Read More

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December 2021

Mast cell activation disease and immunoglobulin deficiency in patients with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorder.

Am J Med Genet C Semin Med Genet 2021 12 7;187(4):473-481. Epub 2021 Nov 7.

Comprehensive Asthma and Allergy, Tarrytown, New York, USA.

Mast cell activation disease (MCAD) includes single organ disease such as asthma, urticaria, and gastroenteritis, as well as multiorgan system involvement such as mast cell activation syndrome and anaphylaxis. Reports link MCAD with hypermobile Ehlers-Danlos syndrome (hEDS), hypermobility spectrum disorder (HSD), and with primary immune deficiencies such as complement and immunoglobulin deficiencies (Ig Def). This study assesses the concurrence of these syndromes. Read More

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December 2021

Advances in assessment of hypermobility-related disorders.

Authors:
Jane V Simmonds

Am J Med Genet C Semin Med Genet 2021 12 6;187(4):453-457. Epub 2021 Nov 6.

Great Ormond Street Institute of Child Health, University College London, London, UK.

There has been increasing recognition in recent years of the prevalence and impact of symptoms which extend beyond the musculoskeletal system on the lives of people with hypermobility-related disorders. This has led researchers to develop more comprehensive assessment tools to help direct and monitor treatment. This article presents some of the latest assessment and diagnostic developments and their implications for practice from a physical therapy perspective. Read More

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December 2021