scholarly journals Molecular Genetics and Pathogenesis of Ehlers–Danlos Syndrome and Related Connective Tissue Disorders

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 547 ◽  
Author(s):  
Marco Ritelli ◽  
Marina Colombi
Keyword(s):  
Connective Tissue ◽  
Genetic Defect ◽  
Joint Hypermobility ◽  
Future Research ◽  
Molecular Testing ◽  
Variable Degree ◽  
Connective Tissue Disorders ◽  
Clinical Genetic ◽  
Ehlers Danlos Syndrome ◽  
Causal Genes

Ehlers–Danlos syndromes (EDS) are a group of heritable connective tissue disorders (HCTDs) characterized by a variable degree of skin hyperextensibility, joint hypermobility and tissue fragility. The current EDS classification distinguishes 13 subtypes and 19 different causal genes mainly involved in collagen and extracellular matrix synthesis and maintenance. EDS need to be differentiated from other HCTDs with a variable clinical overlap including Marfan syndrome and related disorders, some types of skeletal dysplasia and cutis laxa. Clinical recognition of EDS is not always straightforward and for a definite diagnosis, molecular testing can be of great assistance, especially in patients with an uncertain phenotype. Currently, the major challenging task in EDS is to unravel the molecular basis of the hypermobile EDS that is the most frequent form, and for which the diagnosis is only clinical in the absence of any definite laboratory test. This EDS subtype, as well as other EDS-reminiscent phenotypes, are currently investigated worldwide to unravel the primary genetic defect and related pathomechanisms. The research articles, case report, and reviews published in this Special Issue focus on different clinical, genetic and molecular aspects of several EDS subtypes and some related disorders, offering novel findings and future research and nosological perspectives.

scholarly journals A floppy infant without lingual frenulum and kyphoscoliosis: Ehlers Danlos syndrome case report

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Rosaura Conti ◽  
Chiara Zanchi ◽  
Egidio Barbi
Keyword(s):  
Connective Tissue ◽  
Muscular Atrophy ◽  
Neuromuscular Disorders ◽  
Joint Hypermobility ◽  
Mechanical Instability ◽  
Connective Tissue Disorders ◽  
Ehlers Danlos Syndrome ◽  
Lower Lip ◽  
Floppy Infant ◽  
Danlos Syndrome

Abstract Background Ehlers-Danlos syndrome (EDS) represents a group of connective tissue disorders characterized by the fragility of the soft connective tissues resulting in widespread skin, ligament, joint, blood vessel and internal organ involvement. The clinical spectrum is highly variable in terms of clinical features, complications, severity, biochemical characteristics and genes mutations. The kyphoscoliotic type EDS (EDS VIA) is a rare variant of the disease, with an incidence of 1:100.000 live births. EDS VIA presents at birth as severe muscular hypotonia, early onset of progressive kyphoscoliosis, marked hyperelasticity and fragility of the skin with abnormal scarring, severe joint hypermobility, luxations and osteopenia without a tendency to fractures. This condition is due to a mutation in the PLOD1 gene, and less commonly in FKBP14 gene, which results in the erroneous development of collagen molecules with consequent mechanical instability of the affected tissue. Case presentation A female newborn, found to be floppy at birth, presented a remarkable physical examination for joint hypermobility, muscle weakness, hyperelastic skin, a slight curve of the spine, the absence of the inferior labial and lingual frenulum. Due to severe hypotonia, neuromuscular disorders such as Spinal Muscular Atrophy (SMA), genetic diseases such as Prader Willi syndrome (PWS), myopathies and connective tissue disorders were considered in the differential diagnosis. Targeted gene sequencing were performed for SMN1, PLOD1, FKBP14, COL6A1, COL6A2, COL6A3. The urinary lysyl and hydroxy-lysyl pyridinoline ratio was diagnostic before discovering the homozygous duplication in the PLOD1 gene, which confirmed kyphoscoliotic EDS diagnosis. Conclusion In front of a floppy infant, a large variety of disorders should be considered, including some connective diseases. The presence at the birth of kyphoscoliosis, associated with joint hypermobility and the absence of the lingual and lower lip frenulum, should suggest an EDS.

scholarly journals Classification, nosology and diagnostics of Ehlers-Danlos syndrome

2019 ◽  
Vol 5 (2) ◽  
pp. 34-46
Author(s):  
Ben C J Hamel
Keyword(s):  
New York ◽  
Connective Tissue ◽  
Joint Hypermobility ◽  
Multidisciplinary Teams ◽  
Connective Tissue Disorders ◽  
Joint Hypermobility Syndrome ◽  
Ehlers Danlos Syndrome ◽  
Skin Fragility ◽  
Danlos Syndrome ◽  
Heritable Connective Tissue Disorders

Ehlers-Danlos syndrome (EDS) comprises a group of heritable connective tissue disorders which has as cardinal features varying degrees of skin hyperextensibility, joint hypermobility, easy bruising and skin fragility. The 2017 New York nosology distinguishes 13 types of EDS, which all, except hypermobile EDS, have a known molecular basis. Hypermobile EDS is recognized as a common and often disabling disorder, incorporating benign joint hypermobility syndrome. EDS needs to be differentiated from other connective tissue disorders, in particular Marfan syndrome, Loeys-Dietz syndrome and cutis laxa. The frequent types of EDS can be diagnosed after careful history taking and clinical examination, but for definite diagnosis molecular confirmation is needed in all types. Management for EDS patients preferably is provided by multidisciplinary teams in expertise centres. After diagnosing EDS genetic counselling is an essential part of the management of patients and their family.

scholarly journals Ehlers–Danlos Syndrome: Not Just Joint Hypermobility

2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Tina Bregant ◽  
Milica Klopcic Spevak
Keyword(s):  
Back Pain ◽  
Connective Tissue ◽  
Severe Pain ◽  
Joint Hypermobility ◽  
Connective Tissue Disorders ◽  
Skin Texture ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome

Ehlers–Danlos syndrome is an umbrella term for a group of heritable soft connective tissue disorders which is characterized by joint hypermobility, skin texture and elasticity abnormalities, and visceral and vascular fragility or dysfunctions. As the syndrome is rare, it is often underdiagnosed. Patients usually present late, with chronic moderate to severe pain which is attributed to the joint hypermobility and joint subluxations. If the clinician is aware of the syndrome, he/she can identify affected patients in order to prevent complications. We report a 60-year-old woman with arthralgia and back pain lasting for several months and recent metatarsophalangeal luxation of the left toe who was discovered to have Ehlers–Danlos syndrome.

Case 64: Ehlers-Danlos Syndrome and Small Fiber Neuropathy

2019 ◽  
pp. 336-339
Author(s):  
Peter Novak
Keyword(s):  
Connective Tissue ◽  
Autonomic Failure ◽  
Joint Hypermobility ◽  
Anxiety Symptoms ◽  
Small Fiber Neuropathy ◽  
Tilt Test ◽  
Connective Tissue Disorders ◽  
Ehlers Danlos Syndrome ◽  
Small Fiber ◽  
Danlos Syndrome

Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. This patient had severe small fiber neuropathy, likely contributing to her pain complaints. Tilt test was negative, except for anxiety symptoms. There was no evidence of autonomic failure.

scholarly journals Heritable Connective Tissue Disorders in Childhood: Increased Fatigue, Pain, Disability and Decreased General Health

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 831
Author(s):  
Jessica Warnink-Kavelaars ◽  
Lisanne de Koning ◽  
Lies Rombaut ◽  
Mattijs Alsem ◽  
Leonie Menke ◽  
...  
Keyword(s):  
Connective Tissue ◽  
General Health ◽  
Normative Data ◽  
Self Report ◽  
Connective Tissue Disorders ◽  
Ehlers Danlos Syndrome ◽  
Validated Questionnaires ◽  
Pain Disability ◽  
Vas Scores ◽  
Heritable Connective Tissue Disorders

Heritable Connective Tissue Disorders (HCTD) show an overlap in the physical features that can evolve in childhood. It is unclear to what extent children with HCTD experience burden of disease. This study aims to quantify fatigue, pain, disability and general health with standardized validated questionnaires. Methods. This observational, multicenter study included 107 children, aged 4–18 years, with Marfan syndrome (MFS), 58%; Loeys-Dietz syndrome (LDS), 7%; Ehlers-Danlos syndromes (EDS), 8%; and hypermobile Ehlers-Danlos syndrome (hEDS), 27%. The assessments included PROMIS Fatigue Parent–Proxy and Pediatric self-report, pain and general health Visual-Analogue-Scales (VAS) and a Childhood Health Assessment Questionnaire (CHAQ). Results. Compared to normative data, the total HCTD-group showed significantly higher parent-rated fatigue T-scores (M = 53 (SD = 12), p = 0.004, d = 0.3), pain VAS scores (M = 2.8 (SD = 3.1), p < 0.001, d = 1.27), general health VAS scores (M = 2.5 (SD = 1.8), p < 0.001, d = 2.04) and CHAQ disability index scores (M = 0.9 (SD = 0.7), p < 0.001, d = 1.23). HCTD-subgroups showed similar results. The most adverse sequels were reported in children with hEDS, whereas the least were reported in those with MFS. Disability showed significant relationships with fatigue (p < 0.001, rs = 0.68), pain (p < 0.001, rs = 0.64) and general health (p < 0.001, rs = 0.59). Conclusions. Compared to normative data, children and adolescents with HCTD reported increased fatigue, pain, disability and decreased general health, with most differences translating into very large-sized effects. This new knowledge calls for systematic monitoring with standardized validated questionnaires, physical assessments and tailored interventions in clinical care.

scholarly journals Hereditary Connective Tissue Diseases in Young Adult Stroke: A Comprehensive Synthesis

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Olivier M. Vanakker ◽  
Dimitri Hemelsoet ◽  
Anne De Paepe
Keyword(s):  
Connective Tissue ◽  
Metabolic Disorders ◽  
Type Iv Collagen ◽  
Connective Tissue Diseases ◽  
Haemorrhagic Stroke ◽  
Monogenic Disease ◽  
Connective Tissue Disorders ◽  
Ehlers Danlos Syndrome ◽  
Type Iv ◽  
Danlos Syndrome

Though the genetic background of ischaemic and haemorrhagic stroke is often polygenetic or multifactorial, it can in some cases result from a monogenic disease, particularly in young adults. Besides arteriopathies and metabolic disorders, several connective tissue diseases can present with stroke. While some of these diseases have been recognized for decades as causes of stroke, such as the vascular Ehlers-Danlos syndrome, others only recently came to attention as being involved in stroke pathogenesis, such as those related to Type IV collagen. This paper discusses each of these connective tissue disorders and their relation with stroke briefly, emphasizing the main clinical features which can lead to their diagnosis.

Arterial complications in classical Ehlers-Danlos syndrome: a case series

2020 ◽  
Vol 57 (11) ◽  
pp. 769-776
Author(s):  
Chloe Angwin ◽  
Angela F Brady ◽  
F Michael Pope ◽  
Anthony Vandersteen ◽  
Duncan Baker ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Case Series ◽  
Joint Hypermobility ◽  
Vascular Complication ◽  
Aortic Aneurysms ◽  
Vascular Events ◽  
Ehlers Danlos Syndrome ◽  
Arterial Complications ◽  
Arterial Complication ◽  
Increased Risk

BackgroundThe Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders with several recognised types. Patients with a type of EDS have connective tissue abnormalities resulting in a varying degree of joint hypermobility, skin and vascular fragility and generalised tissue friability. Classical EDS (cEDS) typically occurs as a result of dominant pathogenic variants in COL5A1 or COL5A2. The cardinal features of cEDS are hyperextensible skin, atrophic scarring and joint hypermobility. Arterial complications are more characteristically a feature of vascular EDS although individual cases of arterial events in cEDS have been reported.MethodsA cohort of 154 patients with a clinical diagnosis of cEDS from the UK was analysed.ResultsSeven patients (4.5%) with a diagnosis of cEDS (four pathogenic, one likely pathogenic and two variants of uncertain significance in COL5A1) who had experienced arterial complications were identified. Arterial complications mostly involved medium-sized vessels and also two abdominal aortic aneurysms. No unique clinical features were identified in this group of patients.ConclusionThere is a possible increased risk of arterial complications in patients with cEDS, although not well-defined. Clinicians need to be aware of this possibility when presented with a patient with an arterial complication and features of cEDS. Long-term management in families with cEDS and a vascular complication should be individually tailored to the patient’s history and their family’s history of vascular events.

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