scholarly journals Update on Congenital Myopathies in Adulthood

2020 ◽  
Vol 21 (10) ◽  
pp. 3694
Author(s):  
George Konstantinos Papadimas ◽  
Sophia Xirou ◽  
Evangelia Kararizou ◽  
Constantinos Papadopoulos
Keyword(s):  
Muscle Biopsy ◽  
Genetic Basis ◽  
Late Onset ◽  
Congenital Myopathies ◽  
Histopathological Findings ◽  
Muscle Diseases ◽  
Phenotypic Spectrum ◽  
Clinical Presentations ◽  
Genetic Technologies ◽  
Key Features

Congenital myopathies (CMs) constitute a group of heterogenous rare inherited muscle diseases with different incidences. They are traditionally grouped based on characteristic histopathological findings revealed on muscle biopsy. In recent decades, the ever-increasing application of modern genetic technologies has not just improved our understanding of their pathophysiology, but also expanded their phenotypic spectrum and contributed to a more genetically based approach for their classification. Later onset forms of CMs are increasingly recognised. They are often considered milder with slower progression, variable clinical presentations and different modes of inheritance. We reviewed the key features and genetic basis of late onset CMs with a special emphasis on those forms that may first manifest in adulthood.

scholarly journals Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1-disease

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011528
Author(s):  
Andreas Traschütz ◽  
Andrea Cortese ◽  
Selina Reich ◽  
Natalia Dominik ◽  
Jennifer Faber ◽  
...  
Keyword(s):  
Natural History ◽  
Late Onset ◽  
Premature Death ◽  
Cross Sectional ◽  
Treatment Trials ◽  
Disease Spectrum ◽  
Phenotypic Spectrum ◽  
Multisystemic Disease ◽  
Repeat Expansions ◽  
Cerebellar Type

Objective:To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of RFC1-repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS).Methods:Multimodal RFC1 repeat screening (PCR, southern blot, whole-exome/genome (WES/WGS)-based approaches) combined with cross-sectional and longitudinal deep-phenotyping in (i) cross-European cohort A (70 families) with ≥2 features of CANVAS and/or ataxia-with-chronic-cough (ACC); and (ii) Turkish cohort B (105 families) with unselected late-onset ataxia.Results:Prevalence of RFC1-disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1-disease was also identified in Western and Eastern Asians, and even by WES. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (>90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (=overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea and/or dystonia (11%). Ataxia progression was ∼1.3 SARA points/year (32 cross-sectional, 17 longitudinal assessments, follow-up ≤9 years [mean 3.1]), but also included early falls, variable non-linear phases of MSA-C-like progression (SARA 2.5-5.5/year), and premature death. Treatment trials require 330 (1-year-trial) and 132 (2-year-trial) patients in total to detect 50% reduced progression.Conclusions:RFC1-disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes, yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our natural history data help to inform future RFC1-treatment trials.Classification of Evidence:This study provides Class II evidence that RFC1-repeat expansions are associated with CANVAS and ACC.

scholarly journals Leprosy neuropathy: clinical presentations

2013 ◽  
Vol 71 (9B) ◽  
pp. 661-666 ◽  
Author(s):  
Osvaldo J M Nascimento
Keyword(s):  
Late Onset ◽  
Early Recognition ◽  
Skin Lesions ◽  
Multidrug Therapy ◽  
Clinical Presentations ◽  
Peripheral Nerve Involvement ◽  
Inflammatory Neuropathy ◽  
Leprosy Neuropathy ◽  
Autonomic Dysfunctions

Leprosy is a chronic infectious peripheral neuropathy caused by Mycobacterium leprae. The different clinical presentations of the disease are determined by the quality of the host immune response. Early detection of leprosy and treatment by multidrug therapy are the most important steps in preventing deformity and disability. Thus the early recognition of the clinical leprosy presentation is essential. Mononeuritis, mononeuritis multiplex (MM), polyneuritis (MM summation) are the most frequent. The frequent anesthetic skin lesions are absent in the pure neuritic leprosy presentation form. Isolated peripheral nerve involvement is common, including the cranial ones. Arthritic presentation is occasionally seen, usually misdiagnosed as rheumatoid arthritis. Attention should be given to autonomic dysfunctions in leprosy. There are clinical presentations with severe neuropathic pain - painful small-fiber neuropathy. Leprous late-onset neuropathy (LLON) clinical presentation should be considered facing a patient who develop an inflammatory neuropathy many years after a previous skin leprosy treatment.

Late-onset riboflavin transporter deficiency: a treatable mimic of various motor neuropathy aetiologies

2020 ◽  
Vol 92 (1) ◽  
pp. 27-35
Author(s):  
Christophe Carreau ◽  
Charline Benoit ◽  
Guido Ahle ◽  
Cécile Cauquil ◽  
Agathe Roubertie ◽  
...  
Keyword(s):  
Late Onset ◽  
High Dose ◽  
Motor Neuropathy ◽  
Biochemical Tests ◽  
Oral Supplementation ◽  
Clinical Presentations ◽  
Hereditary Motor Neuropathy ◽  
Transporter Deficiency ◽  
Per Oral ◽  
Lateral Sclerosis

ObjectiveRiboflavin transporter deficiencies (RTDs), involving SLC52A3 and SLC52A2 genes, have recently been related to Brown-Vialetto-Van Laere (BVVL) syndrome, a hereditary paediatric condition associating motor neuropathy (MN) and deafness. BVVL/RTD has rarely been reported in adult patients, but is probably underdiagnosed due to poor knowledge and lack of awareness of this form of disease among neurologists. In this study, we aimed to investigate the phenotype and prognosis of RTD patients with late-onset MN.MethodsWe retrospectively collected clinical, biological and electrophysiological data from all French RTD patients with MN onset after 10 years of age (n=6) and extracted data from 19 other similar RTD patients from the literature.ResultsAdult RTD patients with MN had heterogeneous clinical presentations, potentially mimicking amyotrophic lateral sclerosis or distal hereditary motor neuropathy (56%), multinevritis with cranial nerve involvement (16%), Guillain-Barré syndrome (8%) and mixed motor and sensory neuronopathy syndromes (20%, only in SLC52A2 patients). Deafness was often diagnosed before MN (in 44%), but in some patients, onset began only with MN (16%). The pattern of weakness varied widely, and the classic pontobulbar palsy described in BVVL was not constant. Biochemical tests were often normal. The majority of patients improved under riboflavin supplementation (86%).InterpretationWhereas late-onset RTD may mimic different acquired or genetic causes of motor neuropathies, it is a diagnosis not to be missed since high-dose riboflavin per oral supplementation is often highly efficient.

Personality structure in the paranoid psychoses of later life

1993 ◽  
Vol 8 (2) ◽  
pp. 59-66 ◽  
Author(s):  
R Howard ◽  
R Levy
Keyword(s):  
Genetic Basis ◽  
Late Onset ◽  
Later Life ◽  
Personality Structure ◽  
Premorbid Personality ◽  
Paranoid Personality ◽  
Icd 10 ◽  
Personality Disturbance ◽  
Paranoid Psychosis

SummaryAbnormal premorbid personality has long been considered to be an important feature of patients who develop schizophrenia, or schizophrenic-like psychoses late in life. Schizoid and paranoid personality traits in particular are repeatedly reported to have preceded the development of psychosis by many years. Such personality abnormalities have been viewed as part of a schizophrenic spectrum disorder, causally invoked in the aetiology of psychosis, or even regarded as an adaptive protection of vulnerable individuals against psychotic breakdown. An ICD-10 diagnosable personality disorder, however, is seen in only about 50% of patients who develop a paranoid psychosis late in life. The premorbid personality abnormalities encountered in late-onset paranoid states and delusional disorder are different from those reported in schizophrenia and there appears to be a genetic basis for these differences. The role of such personality disturbance in the aetiology of psychosis is controversial but probably only minor.

The potential of new genetic technologies in selecting for stress resistance in pigs

2005 ◽  
Vol 45 (8) ◽  
pp. 775
Author(s):  
C. A. Kerr ◽  
B. M. Hines
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Stress Resistance ◽  
Genetic Basis ◽  
Molecular Mechanisms ◽  
Negative Impact ◽  
Experimental Models ◽  
Genetic Technologies ◽  
On Farm ◽  
Commercial Environment

This paper examines the potential for breeding stress resistance in pigs through an understanding of the physiology of the stress response and its associated genetic basis. Pigs reared in commercial units can encounter numerous concurrent stressors that can have a negative impact on performance and welfare. Stress induces physiological and behavioural responses that are multidimensional, consisting of a complex neuroendocrine and immune signalling milieu. Some stress-related genetic parameters have been identified using conventional genetic approaches applied in experimental models. However, these traits do not capture the complexity of the stress response. As a result, the molecular mechanisms underlying the variation associated with stress resistance in pigs in a commercial environment is poorly understood. Gene expression profiling is a powerful tool that can be applied to systematically elucidate stress response pathways and networks. Consequently, gene expression technologies have been applied to identify some putative stress-regulated genes. Further application of these and more traditional technologies will aid in elucidating stress resistance using gene expression as a measure of phenotypic variation at a molecular level. It is envisaged that in the future, tools for selecting for stress resistance could eventually be applied on-farm to enhance production, health and welfare status.

Regulating Genetic Information—Exploring the Options in Legal Theory

2014 ◽  
Vol 21 (5) ◽  
pp. 425-453 ◽  
Author(s):  
Aisling de Paor
Keyword(s):  
Genetic Information ◽  
Genetic Basis ◽  
Legal Theory ◽  
Personalised Medicine ◽  
Theoretical Perspective ◽  
Genetic Technology ◽  
Regulatory Frameworks ◽  
Technological Advances ◽  
Genetic Technologies ◽  
Genetic Science

Ground-breaking genetic discoveries and technological advances have introduced a new world of genetic exploration, and technological advances have facilitated the discovery of the genetic basis of a myriad of diseases. Genetic testing promises to potentially revolutionise health care and offer the potential of personalised medicine. Genetic technology may also offer the means to detect potential future disabilities. In light of rapid advances in genetic science and technology, questions arise as to whether an appropriate framework exists to protect the interests of individuals, prevent the misuse of genetic information by interested third parties, and also to encourage further advances in genetic science. In consideration of rapidly advancing genetic technologies and the ethical and legal concerns that arise, this article examines the regulation of genetic information, primarily from a theoretical perspective. It explores the preferable mode of regulation and choice of regulatory frameworks in legal theory, including non-discrimination, privacy and property.

scholarly journals Huntington’s Disease in a Patient Misdiagnosed as Conversion Disorder

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
João Machado Nogueira ◽  
Ana Margarida Franco ◽  
Susana Mendes ◽  
Anabela Valadas ◽  
Cristina Semedo ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Psychiatric Symptoms ◽  
Age Of Onset ◽  
Late Onset ◽  
Psychiatric Patients ◽  
Conversion Disorder ◽  
Cag Repeat ◽  
Clinical Assessments ◽  
Clinical Presentations

Huntington’s disease (HD) is an inherited, progressive, and neurodegenerative neuropsychiatric disorder caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide in Interested Transcript (IT) 15 gene on chromosome 4. This pathology typically presents in individuals aged between 30 and 50 years and the age of onset is inversely correlated with the length of the CAG repeat expansion. It is characterized by chorea, cognitive deficits, and psychiatric symptoms. Usually the psychiatric disorders precede motor and cognitive impairment, Major Depressive Disorder and anxiety disorders being the most common presentations. We present a clinical case of a 65-year-old woman admitted to our Psychiatric Acute Unit. During the 6 years preceding the admission, the patient had clinical assessments made several times by different specialties that focused only on isolated symptoms, disregarding the syndrome as a whole. In the course of her last admission, the patient was referred to our Neuropsychiatric Team, which made the provisional diagnosis of late-onset Huntington’s disease, later confirmed by genetic testing. This clinical vignette highlights the importance of a multidisciplinary approach to atypical clinical presentations and raises awareness for the relevance of investigating carefully motor symptoms in psychiatric patients.

scholarly journals Premature Ovarian Insufficiency: New Perspectives on Genetic Cause and Phenotypic Spectrum

2016 ◽  
Vol 37 (6) ◽  
pp. 609-635 ◽  
Author(s):  
Elena J. Tucker ◽  
Sonia R. Grover ◽  
Anne Bachelot ◽  
Philippe Touraine ◽  
Andrew H. Sinclair
Keyword(s):  
Mouse Models ◽  
Genetic Basis ◽  
Current Knowledge ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Activity ◽  
Substantial Evidence ◽  
Ovarian Insufficiency ◽  
Phenotypic Spectrum ◽  
Disease Mechanisms

Abstract Premature ovarian insufficiency (POI) is one form of female infertility, defined by loss of ovarian activity before the age of 40 and characterized by amenorrhea (primary or secondary) with raised gonadotropins and low estradiol. POI affects up to one in 100 females, including one in 1000 before the age of 30. Substantial evidence suggests a genetic basis for POI; however, the majority of cases remain unexplained, indicating that genes likely to be associated with this condition are yet to be discovered. This review discusses the current knowledge of the genetic basis of POI. We highlight genes typically known to cause syndromic POI that can be responsible for isolated POI. The role of mouse models in understanding POI pathogenesis is discussed, and a thorough list of candidate POI genes is provided. Identifying a genetic basis for POI has multiple advantages, such as enabling the identification of presymptomatic family members who can be offered counseling and cryopreservation of eggs before depletion, enabling personalized treatment based on the cause of an individual's condition, and providing better understanding of disease mechanisms that ultimately aid the development of improved treatments.

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