Classical Ehlers-Danlos syndrome: clinical, Histological and ultrastructural aspects

Bicca, Eduardo de Barros Coelho; Almeida, Fabiano Bonow de; Pinto, Giselle Martins; Castro, Luis Antônio Suíta de; Almeida, Hiram Larangeira de

doi:10.1590/s0365-05962011000700043

Cited by 10 publications

(12 citation statements)

References 13 publications

(29 reference statements)

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“…Interestingly, investigation showed disorganisation, variation of fibril diameter, and irregular fibril outlines. However, this patient did not have molecular investigations, and the underlying molecular basis is unknown [18].…”

Section: Discussionmentioning

confidence: 99%

Absence of Collagen Flowers on Electron Microscopy and Identification of (Likely) Pathogenic COL5A1 Variants in Two Patients

Angwin

Brady

Colombi

et al. 2019

Genes

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Two probands are reported with pathogenic and likely pathogenic COL5A1 variants (frameshift and splice site) in whom no collagen flowers have been identified with transmission electron microscopy (TEM). One proband fulfils the clinical criteria for classical Ehlers-Danlos syndrome (cEDS) while the other does not and presents with a vascular complication. This case report highlights the significant intrafamilial variability within the cEDS phenotype and demonstrates that patients with pathogenic COL5A1 variants can have an absence of collagen flowers on TEM skin biopsy analysis. This has not been previously reported in the literature and is important when evaluating the significance of a TEM result in patients with clinically suspected cEDS and underscores the relevance of molecular analysis.

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Section: Discussionmentioning

confidence: 99%

Absence of Collagen Flowers on Electron Microscopy and Identification of (Likely) Pathogenic COL5A1 Variants in Two Patients

Angwin

Brady

Colombi

et al. 2019

Genes

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“…Data were derived from clinical notes regarding prior investigations, clinical features, biopsy TEM reports, biochemical and molecular investigation, and definitive diagnoses. A definitive 31,38 vascular EDS and hypermobility type EDS (hEDS). 37 Collagen fibres are typically organized into linear bundles of fibrils, probably to compound tensile strength.…”

Section: Methodsmentioning

confidence: 99%

“…27 Variable diameter has also been reported in vascular EDS 28,29 and classical (cEDS). 15,[30][31][32] A 1982 paper reported variable or abnormal diameters in all subtypes of EDS and in a number of other inherited connective tissue disorders; however, no molecular testing was available to this group. 33 (b) Cross-section illustrating the appearance of collagen flowers.…”

Section: Patientsmentioning

confidence: 99%

Electron microscopy in the diagnosis of Ehlers–Danlos syndromes: correlation with clinical and genetic investigations

et al. 2019

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Summary Background The Ehlers–Danlos syndromes (EDS) consist of 13 subtypes with overlapping features including joint hypermobility, skin and vascular fragility and generalized connective tissue friability. As DNA analysis has become the gold standard for investigation of EDS, transmission electron microscopy (TEM) in clinical practice is decreasing. However, owing to the use of next‐generation sequencing, the frequency of variants of uncertain significance (VUS) identified using DNA analysis is increasing. We hypothesized that TEM can provide evidence for or against pathogenicity of VUS. Objectives The aim of this study was to evaluate the role of TEM in the diagnosis of EDS subtypes. Methods Data were collected from patients who underwent a skin biopsy between October 2012 and March 2017 at the London EDS National Diagnostic Service. TEM biopsies were categorized as ‘normal’ or ‘abnormal’ according to the description and conclusion in the TEM reports. Definitive diagnoses were reached via a combination of clinical features, structural and functional studies and DNA investigations. Results The analysis included 177 patients, comprising 30 abnormal and 147 normal TEM reports. A definitive diagnosis of monogenic EDS subtypes was made in 24 patients. Overall, 17 of these 24 patients (71%) had an abnormal biopsy report and seven (29%) had a normal biopsy report. No TEM findings were specifically associated with any EDS subtype, although collagen flowers were present in most patients with a genetically confirmed diagnosis of classical EDS. Conclusions TEM analysis of collagen structure may have the potential to provide evidence for or against the pathogenicity of a VUS, but more work is needed to establish a clear role for TEM in this process. What's already known about this topic? Collagen fibril abnormalities can be seen in several Ehlers–Danlos syndrome (EDS) subtypes. What does this study add? This study provides clinical data, transmission electron microscopy (TEM) data and molecular data of one of the largest groups of patients suspected to have a monogenetic EDS subtype. No TEM findings were specifically associated with an EDS subtype. There was a higher percentage (71%) of abnormal biopsy findings in patients with a definitive diagnosis of a monogenetic EDS subtype and where a class 4/5 genetic variant was present.

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“… 1 - 4 Constitutive fragility of the connective tissue may permit penetration of fat into upper layers of the skin, what would explain its association with congenital defects of the collagen, such as Ehlers-Danlos syndrome (EDS). 1 - 5 …”

mentioning

confidence: 99%

“…2 Some cases have a familial pattern, and others occur simultaneously to some diseases such as Prader-Willi syndrome and, as pointed out earlier, EDS. 1 , 3 - 5 …”

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confidence: 99%

Piezogenic Pedal Papules

Rocha

Fernandes

Prates

2015

An. Bras. Dermatol.

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Classical Ehlers-Danlos syndrome: clinical, Histological and ultrastructural aspects

Cited by 10 publications

References 13 publications

Absence of Collagen Flowers on Electron Microscopy and Identification of (Likely) Pathogenic COL5A1 Variants in Two Patients

Absence of Collagen Flowers on Electron Microscopy and Identification of (Likely) Pathogenic COL5A1 Variants in Two Patients

Electron microscopy in the diagnosis of Ehlers–Danlos syndromes: correlation with clinical and genetic investigations

Piezogenic Pedal Papules

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