scholarly journals Genetic testing for vascular Ehlers-Danlos syndrome and other variants with fragility of the middle arteries

2018 ◽  
Vol 2 (s1) ◽  
pp. 42-44
Author(s):  
Yeltay Rakhmanov ◽  
Paolo Enrico Maltese ◽  
Alice Bruson ◽  
Marco Castori ◽  
Tommaso Beccari ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Clinical Trials ◽  
Vascular Involvement ◽  
Molecular Testing ◽  
Connective Tissue Disorders ◽  
Ehlers Danlos Syndrome ◽  
Recurrent Mutations ◽  
Gene Test ◽  
Danlos Syndrome

Abstract Ehlers-Danlos syndrome (EDS) is an umbrella term for various inherited connective tissue disorders associated with mutations in genes involved in extracellular matrix formation. “The 2017 International Classification of Ehlers-Danlos Syndromes and related disorders” identifies 13 clinical types with mutations in 19 distinct genes. The present module focuses on forms with major vascular involvement: vascular EDS (vEDS) caused by heterozygous mutations in COL3A1, “vascular-like” EDS (vlEDS) caused by recurrent mutations in COL1A1, classical EDS with vascular fragility associated with heterozygous mutations in COL5A1, and kyphoscoliotic EDS associated with recessive variations in PLOD1 and FKBP14. The overall prevalence of EDS is estimated between 1/10,000 and 1/25,000 and vEDS accounts for about 5 to 10% of all EDS cases. This Utility Gene Test was prepared on the basis of an analysis of the literature and existing diagnostic protocols. Molecular testing is useful for diagnosis confirmation, as well as differential diagnosis, appropriate genetic counselling and access to clinical trials.

scholarly journals Surgical-orthodontic treatment in patients with Ehlers–Danlos syndrome: a report of two familial cases

2020 ◽  
Vol 26 (1) ◽  
pp. 5
Author(s):  
Hippolyte Chapuis ◽  
Arnaud Peyrolade ◽  
Ahmed Féki ◽  
François Clauss ◽  
Fabien Bornert
Keyword(s):  
Orthodontic Treatment ◽  
Clinical Symptoms ◽  
Genetic Mutation ◽  
Therapeutic Approaches ◽  
Connective Tissue Disorders ◽  
Ehlers Danlos Syndrome ◽  
Familial Form ◽  
Danlos Syndrome

Introduction: Ehlers–Danlos syndromes (EDS) are a group of rare inherited connective tissue disorders that affect the synthesis and structure of collagen in a ubiquitous manner. The clinical presentation can vary according to the associated genetic mutation. The 2017 international classification of EDS describes 13 types of EDS. Observation: The first part of this paper describes the surgical-orthodontic treatment for two sisters affected by a common and familial form of EDS, with a follow-up period of 8 years. The main symptoms were agenesis, impacted teeth, and delayed eruptions. Discussion: The second part proposes a review of oro-dental manifestations and discusses therapeutic approaches for patients with EDS. Conclusion: EDS can affect the oro-dental region with numerous consequences. Recognition of clinical symptoms and radiological signs is essential to provide appropriate dental care. Moreover, complete clinical and radiological assessment can allow early diagnosis of EDS.

scholarly journals New principles of diagnosis and classification of the Ehlers-Danlos syndrome

2018 ◽  
Vol 9 (1) ◽  
pp. 118-125
Author(s):  
Vadim G. Arsentev ◽  
Tamara I. Kadurina ◽  
Larisa N. Abbakumova
Keyword(s):  
Connective Tissue ◽  
Diagnostic Criteria ◽  
Clinical Picture ◽  
Clinical Signs ◽  
Connective Tissue Disorders ◽  
Ehlers Danlos Syndrome ◽  
Dominant Type ◽  
Monogenic Diseases ◽  
Danlos Syndrome

Ehlers-Danlos syndrome (EDS) is a heterogeneous group of monogenic diseases caused by a violation of collagen metabolism, the structure and function of myomatrix and the synthesis of proteoglycans. This pathology is characteri zed by hyperelasticity of the skin, subcutaneous globules, overextension of the joints, tissue vulnerability and hemorrhagic syndrome. EDS is one of the seven hereditary connective tissue disorders for which international diagnostic criteria are met. More than 30 years ago, the so-called Berlin nosology of hereditary connective tissue disorders was first compiled and approved (1986). For a long time, doctors used the “Villefranche Nosology” classification of EDS, adopted in 1998 and divided the disease into 6 types. The new criteria were published by the International Committee of Experts in 2017. In the clinical classification of EDS, 13 types with different inheritance, clinical features and biochemical defects are described. In most cases, it is inherited by an autosomal dominant type. True prevalence is unknown due to the complexity of verification and a large number of light forms, the frequency of diagnosed cases is 1 : 5000 births, severe forms are rare (1 : 100 000). Diagnosis of this syndromeis also based on the diagnostic criteria of the international classification. The lecture presents new data on classification diagnostic criteria of EDS, polymorphism of the clinical picture, genetic heterogeneity, the main principles of treatment of the disease. The new classification criteria take into account, in the main, the features of the clinical picture, they did not simplify the diagnosis, but they increased the specificity and increased the significance of the clinical and anamnestic features. The scope of the examination is determined by the presence of leading clinical signs. The genealogical examination and molecular genetic methods of diagnostics are of great importance.

scholarly journals Congenital Disorders of Deficiency in Glycosaminoglycan Biosynthesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuji Mizumoto ◽  
Shuhei Yamada
Keyword(s):  
Extracellular Matrix ◽  
Dermatan Sulfate ◽  
Congenital Disorders ◽  
Connective Tissue Disorders ◽  
Ehlers Danlos Syndrome ◽  
Core Proteins ◽  
Multiple Exostoses ◽  
Extracellular Matrix Components ◽  
Immune Deficiencies ◽  
Danlos Syndrome

Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, and heparan sulfate are covalently attached to specific core proteins to form proteoglycans, which are distributed at the cell surface as well as in the extracellular matrix. Proteoglycans and GAGs have been demonstrated to exhibit a variety of physiological functions such as construction of the extracellular matrix, tissue development, and cell signaling through interactions with extracellular matrix components, morphogens, cytokines, and growth factors. Not only connective tissue disorders including skeletal dysplasia, chondrodysplasia, multiple exostoses, and Ehlers-Danlos syndrome, but also heart and kidney defects, immune deficiencies, and neurological abnormalities have been shown to be caused by defects in GAGs as well as core proteins of proteoglycans. These findings indicate that GAGs and proteoglycans are essential for human development in major organs. The glycobiological aspects of congenital disorders caused by defects in GAG-biosynthetic enzymes including specific glysocyltransferases, epimerases, and sulfotransferases, in addition to core proteins of proteoglycans will be comprehensively discussed based on the literature to date.

Psychiatric Manifestations of Ehlers-Danlos Syndrome in Adolescents: A Case Report and Literature Review

2020 ◽  
Vol 16 ◽  
Author(s):  
Daisy Vyas Shirk ◽  
Sarah D. Williams
Keyword(s):  
Chronic Pain ◽  
Literature Review ◽  
Literature Search ◽  
Web Search ◽  
Psychiatric Symptoms ◽  
Connective Tissue Disorders ◽  
Ehlers Danlos Syndrome ◽  
Symptoms Of Depression ◽  
Psychiatric Manifestations ◽  
Danlos Syndrome

Background: Ehlers-Danlos Syndromes (EDS) comprise a group of heterogeneous hereditary connective tissue disorders [1, 2]. Psychiatric disorders such as depression, anxiety, panic disorder, agoraphobia, schizophrenia, neurodevelopmental disorders, personality disorder, eating disorders, substance misuse and interpersonal issues have been reported in the literature to be associated with EDS [1-3]. Objectives: The case of a 15-year -old male who was hospitalized after a suicide attempt by gunshot was discovered to have symptoms suggestive of EDS is presented in this paper along with the results of a literature search of psychiatric manifestations of EDS in children and adolescents. Methods: Literature review was conducted on the UpToDate website on March 11, 2020 to review symptoms of EhlersDanlos Syndrome for the purpose of preliminary diagnosis of this patient. Additional literature search was conducted on PubMed on 4/2/20 at 12:10 P.M. and on 4/9/20 at 10:51 P.M. and on the search engine Google on 4/2/20 at 12:25 P.M. On May 11, 2020 at 2 P.M., another web search was conducted with review of 6 different websites pertaining to EhlersDanlos Syndrome. Results: A systematic review of psychiatric manifestations of Ehlers-Danlos Syndromes revealed a strong incidence of psychiatric symptoms. Conclusion: Our patient’s psychiatric symptoms of depression, suicidal ideations, anxiety and social and educational struggles may have been at least partially due to chronic pain- abdominal, headache and musculoskeletal, and social ostracization associated with Ehlers-Danlos Syndrome. Education regarding this illness helped our patient’s recovery as he came to understand why he was so “odd” and the cause of his multisystemic chronic pain.

scholarly journals Pain Symptomatology and Management in Pediatric Ehlers–Danlos Syndrome: A Review

Children ◽  
2020 ◽  
Vol 7 (9) ◽  
pp. 146
Author(s):  
Estée C. H. Feldman ◽  
Daniel P. Hivick ◽  
P. Maxwell Slepian ◽  
Susan T. Tran ◽  
Pradeep Chopra ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Psychological Interventions ◽  
Pediatric Pain ◽  
Connective Tissue Disorders ◽  
Ehlers Danlos Syndrome ◽  
Major Criterion ◽  
Pain Characteristics ◽  
The Relationship ◽  
Danlos Syndrome

Ehlers–Danlos syndromes (EDS) are a group of connective tissue disorders that manifest with hyperextensibility of joints and skin, and general tissue fragility. While not a major criterion for clinical diagnosis, pain is a frequently endorsed symptom across subtypes of EDS. As such, the present review aims to summarize research to date on pain characteristics and management, and the relationship between such pain symptomatology and quality of life in pediatric EDS. Characteristics of pain, including theorized etiology, relative intensity and extent of pain are described, as well as descriptions of frequently endorsed pain sites (musculoskeletal, and non-musculoskeletal). Interventions related to the management of musculoskeletal (e.g., pharmaceutical intervention, physical therapy) and non-musculoskeletal pain (e.g., pharmaceutical and psychological interventions) are discussed, highlighting the need for additional research related to pediatric pain management in the context of hypermobility syndromes. In addition, the relationship between pain in pediatric EDS and quality of life is described. Finally, limitations of literature to date are described and recommendations for future lines of research are outlined.

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.

scholarly journals Ehlers–Danlos syndrome: how to diagnose and when to perform genetic tests

2014 ◽  
Vol 100 (1) ◽  
pp. 57-61 ◽  
Author(s):  
Glenda Sobey
Keyword(s):  
Genetic Basis ◽  
Correct Diagnosis ◽  
Clinical Signs ◽  
Accurate Diagnosis ◽  
Connective Tissue Disorders ◽  
Internal Organs ◽  
Ehlers Danlos Syndrome ◽  
Starting Point ◽  
Life Threatening ◽  
Danlos Syndrome

The term Ehlers–Danlos syndrome (EDS) encompasses a group of inherited connective tissue disorders. The manifestations of EDS can be seen in skin, joints, blood vessels and internal organs and vary from mild to severe and life threatening. Each subtype is a separate and different condition. The genetic basis of many subtypes has now been elucidated, confirming heterogeneity. An awareness of the different conditions within this group is the starting point towards accurate diagnosis. Accurate elicitation of history and clinical signs is vital in selecting the correct confirmatory investigation. Skin biopsy with electron microscopy can be helpful in the decision process of whether and when to perform genetic testing. Correct diagnosis within the EDSs allows targeted management, family screening and prenatal diagnosis.

scholarly journals Abnormal type III collagen produced by an exon-17-skipping mutation of the COL3A1 gene in Ehlers-Danlos syndrome type IV is not incorporated into the extracellular matrix

1995 ◽  
Vol 311 (3) ◽  
pp. 939-943 ◽  
Author(s):  
A A Chiodo ◽  
D O Sillence ◽  
W G Cole ◽  
J F Bateman
Keyword(s):  
Extracellular Matrix ◽  
Triple Helix ◽  
Type Iii Collagen ◽  
Syndrome Type ◽  
Ehlers Danlos Syndrome ◽  
Type Iii ◽  
Type Iv ◽  
Col3a1 Gene ◽  
Collagen Molecules ◽  
Danlos Syndrome

A novel heterozygous mutation of the COL3A1 gene that encodes the alpha 1(III) chains of type III collagen was identified in a family with the acrogeric form of Ehlers-Danlos syndrome type IV (EDS-IV). Cultured dermal fibroblasts produced normal and shortened alpha 1(III) chains. The triple helix of the latter chain was shortened owing to a 33 amino acid deletion of Gly-184 to Pro-216. The corresponding region of cDNA lacked 99 base pairs from nucleotides 1051 to 1149. The deletions corresponded exactly to the normal sequence encoded by exon 17 of the COL3A1 gene. The proband was heterozygous for a T to G transversion at position +2 of intron 17, which resulted in skipping of exon 17. The splicing defect was not corrected by growing the fibroblasts at 33 degrees C and no other splicing variants were identified at 33 or 37 degrees C. The affected brother had the same mutation but his unaffected mother did not. Heterotrimeric type III collagen molecules containing normal and mutant chains were retained within the cell. The mutant homotrimeric molecules were modified and secreted normally and were thermally stable. These normal characteristics of the mutant homotrimers suggested that the loss of ten Gly-Xaa-Yaa triplets (where Gly-Xaa-Yaa is a repetitive amino acid triplet structure in which Xaa and Yaa are other amino acids, proline and hydroxyproline being more common in the Yaa position) did not adversely affect the formation and stability of the triple helix or the structural requirements for secretion. However, the mutant homotrimers were not incorporated into the extracellular matrix of an in vitro model of EDS-IV dermis. The EDS-IV phenotype in this family was probably due to a deficiency in the amount of normal type III collagen available for formation of the heterotypic collagen fibrils of the extracellular matrix. Intracellular and extracellular quality-control mechanisms prevented the incorporation of heterotrimeric and homotrimeric mutant type III collagen molecules into the cross-linked extracellular matrix.

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