scholarly journals Mechanisms of disease and clinical features of mutations of the gene for mitofusin 2: an important cause of hereditary peripheral neuropathy with striking clinical variability in children and adults

2010 ◽  
Vol 52 (4) ◽  
pp. 328-330 ◽  
Author(s):  
ROBERT OUVRIER ◽  
SIMON GREW
Keyword(s):  
Peripheral Neuropathy ◽  
Clinical Features ◽  
Mitofusin 2 ◽  
Clinical Variability ◽  
Hereditary Peripheral Neuropathy

scholarly journals Quantifying the Genetic Basis of Marfan Syndrome Clinical Variability

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 574
Author(s):  
Thomas Grange ◽  
Mélodie Aubart ◽  
Maud Langeois ◽  
Louise Benarroch ◽  
Pauline Arnaud ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Clinical Features ◽  
Familial Aggregation ◽  
Phenotypic Variability ◽  
Connective Tissue Disorder ◽  
Clinical Feature ◽  
Phenotypic Variance ◽  
Genetic Modifiers ◽  
Clinical Variability ◽  
New Strategy

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with considerable inter- and intra-familial clinical variability. The contribution of inherited modifiers to variability has not been quantified. We analyzed the distribution of 23 clinical features in 1306 well-phenotyped MFS patients carrying FBN1 mutations. We found strong correlations between features within the same system (i.e., ophthalmology vs. skeletal vs. cardiovascular) suggesting common underlying determinants, while features belonging to different systems were largely uncorrelated. We adapted a classical quantitative genetics model to estimate the heritability of each clinical feature from phenotypic correlations between relatives. Most clinical features showed strong familial aggregation and high heritability. We found a significant contribution by the major locus on the phenotypic variance only for ectopia lentis using a new strategy. Finally, we found evidence for the “Carter effect” in the MFS cardiovascular phenotype, which supports a polygenic model for MFS cardiovascular variability and indicates additional risk for children of MFS mothers with an aortic event. Our results demonstrate that an important part of the phenotypic variability in MFS is under the control of inherited modifiers, widely shared between features within the same system, but not among different systems. Further research must be performed to identify genetic modifiers of MFS severity.

Clinical features and outcomes from the Singapore Sjögren's syndrome study

Lupus ◽  
2020 ◽  
pp. 096120332097693
Author(s):  
Jeggrey Kay-Wee Kam ◽  
Natasha Charan ◽  
Rachel Wei-Li Leong ◽  
Zhi-Wen Loh ◽  
Bernard Yu-Hor Thong
Keyword(s):  
Nervous System ◽  
Peripheral Neuropathy ◽  
Sjögren’S Syndrome ◽  
Clinical Features ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Mononeuritis Multiplex ◽  
Glandular Enlargement ◽  
Sjögren‘S Syndrome

Objective To study the clinical features, treatment and outcomes of primary Sjögren's Syndrome (pSS) in a Singapore cohort from an outpatient rheumatology clinic. Methods Computerised Physician Order entry records of patients who fulfilled the 2016 ACR-EULAR classification criteria for pSS between 1993 and 2013 were retrospectively analysed. Results There were 102 patients, of which 96 (94.1%) were females, and 91 (89.2%) Chinese. Mean age at diagnosis was 49.3 ± 11.8 years, mean disease duration was 9.0 ± 4.6 years. The most common manifestations were keratoconjunctivitis sicca (99.0%), xerostomia (96.1%), arthralgia/arthritis (56.9%). Exocrine glandular enlargement comprised parotidomegaly (28, 27.5%), with concurrent submandibular and lacrimal gland enlargement in one. The nervous system (15.7%) was the most commonly affected internal organ, with peripheral nervous system (peripheral neuropathy, mononeuritis multiplex) involvement more common than central. Hydroxychloroquine was most frequently used (88.2%), followed by methotrexate (7.8%) and azathioprine (6.9%). Pulsed intravenous (IV) methylprednisolone 500 mg/day for 3 days was used in 5 patients followed by oral (4) or IV cyclophosphamide (1) for cardiomyopathy and interstitial lung disease (1), and neurological involvement (4). These comprised neuromyelitis optica, transverse myelopathy, cranial neuropathy, mononeuritis multiplex and/or peripheral neuropathy alone or in combination. Intravenous immunoglobulins (2.0%) was used for sensory neuropathy and mononeuritis multiplex; rituximab (1.0%) in 1 patient for treatment of non-Hodgkin’s B-cell lymphoma. There were no deaths. Conclusion Musculoskeletal manifestations were common, with the nervous system (peripheral more than central) the most common internal organ involved. Lymphoma was uncommon despite up to one-third of the cohort developing glandular enlargement.

scholarly journals Pes cavus and hereditary neuropathies: when a relationship should be suspected

2010 ◽  
Vol 11 (4) ◽  
pp. 195-201 ◽  
Author(s):  
S. Piazza ◽  
G. Ricci ◽  
E. Caldarazzo Ienco ◽  
C. Carlesi ◽  
L. Volpi ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Foot Deformities ◽  
Peripheral Neuropathies ◽  
Pes Cavus ◽  
Molecular Features ◽  
Distal Muscle ◽  
Hammer Toes ◽  
The Common ◽  
Hereditary Peripheral Neuropathy ◽  
Intrinsic Muscles

Abstract The hereditary peripheral neuropathies are a clinically and genetically heterogeneous group of diseases of the peripheral nervous system. Foot deformities, including the common pes cavus, but also hammer toes and twisting of the ankle, are frequently present in patients with hereditary peripheral neuropathy, and often represent one of the first signs of the disease. Pes cavus in hereditary peripheral neuropathies is caused by imbalance between the intrinsic muscles of the foot and the muscles of the leg. Accurate clinical evaluation in patients with pes cavus is necessary to exclude or confirm the presence of peripheral neuropathy. Hereditary peripheral neuropathies should be suspected in those cases with bilateral foot deformities, in the presence of family history for pes cavus and/or gait impairment, and in the presence of neurological symptoms or signs, such as distal muscle hypotrophy of limbs. Herein, we review the hereditary peripheral neuropathies in which pes cavus plays a key role as a “spy sign,” discussing the clinical and molecular features of these disorders to highlight the importance of pes cavus as a helpful clinical sign in these rare diseases.

The Complex Clinical and Genetic Landscape of Hereditary Peripheral Neuropathy

2021 ◽  
Vol 16 (1) ◽  
pp. 487-509
Author(s):  
Soumitra Ghosh ◽  
Warren G. Tourtellotte
Keyword(s):  
Peripheral Neuropathy ◽  
Sensory Neurons ◽  
Neurological Disorders ◽  
Axonal Degeneration ◽  
Early Age ◽  
Single Mutation ◽  
Disease Phenotype ◽  
Genetic Landscape ◽  
Hereditary Peripheral Neuropathy ◽  
Generation Sequencing

Hereditary peripheral neuropathy (HPN) is a complex group of neurological disorders caused by mutations in genes expressed by neurons and Schwann cells. The inheritance of a single mutation or multiple mutations in several genes leads to disease phenotype. Patients exhibit symptoms during development, at an early age or later in adulthood. Most of the mechanistic understanding about these neuropathies comes from animal models and histopathological analyses of postmortem human tissues. Diagnosis is often very complex due to the heterogeneity and overlap in symptoms and the frequent overlap between various genes and different mutations they possess. Some symptoms in HPN are common through different subtypes such as axonal degeneration, demyelination, and loss of motor and sensory neurons, leading to similar physiologic abnormalities. Recent advances in gene-targeted therapies, genetic engineering, and next-generation sequencing have augmented our understanding of the underlying pathogenetic mechanisms of HPN.

Loss‐of‐function of EBP50 is a new cause of hereditary peripheral neuropathy: EBP50 functions in peripheral nerve system

Glia ◽  
2020 ◽  
Vol 68 (9) ◽  
pp. 1794-1809 ◽  
Author(s):  
Gyun Jee Song ◽  
Deepak Prasad Gupta ◽  
Md Habibur Rahman ◽  
Hwan Tae Park ◽  
Imad Al Ghouleh ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Peripheral Nerve ◽  
Loss Of Function ◽  
Peripheral Nerve System ◽  
Hereditary Peripheral Neuropathy ◽  
Nerve System

Neuropathy of Connective Tissue Diseases and Other Systemic Diseases

2019 ◽  
Vol 39 (05) ◽  
pp. 651-668
Author(s):  
Peter H. Jin ◽  
Susan C. Shin
Keyword(s):  
Peripheral Neuropathy ◽  
Connective Tissue ◽  
Clinical Features ◽  
Connective Tissue Diseases ◽  
Chemotherapeutic Agents ◽  
Nutritional Deficiencies ◽  
Systemic Diseases ◽  
Monoclonal Gammopathies ◽  
Diagnosis And Management

AbstractPeripheral neuropathy is associated with numerous systemic diseases. It is often the heralding finding, which can lead to earlier diagnoses and better outcomes. An understanding of the epidemiology and clinical features of these diseases is paramount to their diagnosis and management. This article will focus on neuropathy associated with connective tissue diseases, monoclonal gammopathies, paraneoplastic disorders, medications including chemotherapeutic agents, nutritional deficiencies, alcohol, and toxins.

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