Vascular Ehlers-Danlos syndrome in children: evaluating the importance of diagnosis and follow-up during childhood.

Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder predominantly caused by pathogenic COL3A1 variants. Characteristic arterial and intestinal fragility and generalised severe tissue friability can lead to clinical events from childhood. We highlight a paucity of literature regarding children diagnosed with vEDS, possibly explained by a restraint in predictive testing, and present data on 63 individuals (23 index cases) with a clinical and genetic diagnosis of vEDS in childhood (<18 years) to address this.

Non-genetic diagnostic investigations in monogenic Ehlers-Danlos syndromes.

With increased application of Next Generation Sequencing (NGS) in the diagnosis of monogenic Ehlers-Danlos syndromes, there is an increased probability to identify variants of unknown significance. Additionally, in some cases no genetic alteration may be identified whilst there is a strong clinical suspicion on a monogenic EDS type. The diagnostic value of non-genetic investigations, which prior to NGS were quite commonly used to support the clinical diagnosis of monogenic EDS types, is explored.

Clinical diagnosis of the monogenic Ehlers-Danlos syndromes.

Monogenic Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue conditions that are clinically characterised by joint hypermobility, skin hyperextensibility and/or fragility, and generalised tissue fragility. Gene panel testing with massively parallel sequencing is currently gold standard to confirm diagnoses of the monogenic EDS types. We aim to report on the (combination of) clinical features of the monogenic EDS types through text and photographs, to aid clinical diagnosis as despite the significant progress in genetic testing possibilities, a thorough clinical assessment which includes medical history, family history and physical examination remains important in the diagnostic process.

Letter to the editor: Re: Pathogenic mechanisms of osteogenesis imperfecta, evidence for classification.

A paper published in Orphanet Journal of Rare Diseases proposes a new classification of osteogenesis imperfecta (OI) based upon underlying pathological mechanisms. The proposed numbering of OI types conflicts with the currently used numbering and is likely to lead to confusion. In addition, classification of OI according to underlying pathogenic mechanisms is not novel.

Ehlers-Danlos syndromes: importance of defining the type.

Ehlers-Danlos syndromes (EDS) is an umbrella term describing 14 types, of which 13 are rare and monogenic, with overlapping features of joint hypermobility, skin, and vascular fragility, and generalised connective tissue friability. Hypermobile EDS currently has no identified genetic cause. Most of the rare monogenic EDS types can have neurological features, which are often part of major or minor diagnostic criteria for each type.

Familial hepatic rupture in vascular Ehlers-Danlos syndrome in pregnancy with atypical thromboses.

This case highlights the importance of genetic testing over fibroblast testing and presents the first published thromboelastometry data in vascular Ehlers-Danlos syndrome.

Case report: Two individuals with -related classical-like EDS: Further clinical characterisation and description of novel variants.

-related classical-like EDS (clEDS type 2) is a rare type of Ehlers-Danlos syndrome (EDS) that was first reported in 2016. There are overlapping clinical features with -related classical-like EDS (or clEDS type 1), including skin hyperextensibility, joint hypermobility, and easy bruising. There are currently nine reported individuals with -related clEDS type 2.

An exemplary model of genetic counselling for highly specialised services.

With genomic testing being increasingly integrated into every day clinical practice and a wide range of practitioners ordering genetic tests, it is important that the scope of the genetic counselling role continues to evolve alongside these changes. We present an exemplary role for genetic counsellors in a highly specialised service within England's National Health Service for people who have or are suspected to have rare genetic types of Ehlers Danlos syndrome. The service employs genetic counsellors and consultants from the fields of genetics and dermatology.

Amniotic band sequence in vascular Ehlers-Danlos Syndrome (EDS): Experience of the EDS National Diagnostic Services in the UK.

The association between vascular Ehlers-Danlos Syndrome (vEDS) and amniotic band sequence (ABS) has been previously reported in the literature, mostly in single patient case reports. Here, we aim to extend the current knowledge of this association through a case series of five unrelated individuals with ABS in association with molecularly confirmed vEDS, in addition to undertaking a comprehensive literature review. All the individuals were recruited through the EDS national diagnostic service in the UK following appropriate history, physical examination and genetic investigations.

Oral characteristics in adult individuals with periodontal Ehlers-Danlos syndrome.

Aim: Periodontal Ehlers-Danlos syndrome (pEDS) is a monogenic type of Ehlers-Danlos syndrome characterized by periodontal destruction at a young age. The present study aimed to document the oral phenotype of pEDS based on prospective clinical investigations.

Materials And Methods: Thirty-five adult individuals from 13 families with a clinically and genetically confirmed diagnosis of pEDS underwent a systematic oral assessment.

Atypical variants in COL1A1 and COL3A1 associated with classical and vascular Ehlers-Danlos syndrome overlap phenotypes: expanding the clinical phenotype based on additional case reports.

The vast majority of reported (likely) pathogenic missense variants in the genes coding for the fibrillar collagens leads to the substitution of one of the obligatory glycine residues in the Gly-Xaa-Yaa repeat sequence of the triple helical domain. Their phenotypic consequences and deleterious effects have been well-documented. However, with increasing access to molecular diagnostic testing based on next-generation sequencing techniques, such as sequencing of multi-gene panels and whole-exome sequencing, non-glycine substitutions are more frequently identified in individuals suspected to have a heritable collagen disorder, but their pathogenic effect is often difficult to predict.

Fractures following pregnancy in Osteogenesis imperfecta - A self-controlled case series using Danish Health Registers.

Osteogenesis imperfecta (OI) is a rare inherited connective tissue disorder with considerable clinical and genetic heterogeneity. The clinical hallmark of OI is liability to fractures due to reduced bone strength. Pregnancy and lactation are periods of increased calcium demand resulting in a decrease in maternal bone mineral density (BMD).

Bi-allelic variants in the ER quality-control mannosidase gene EDEM3 cause a congenital disorder of glycosylation.

EDEM3 encodes a protein that converts ManGlcNAc isomer B to ManGlcNAc. It is involved in the endoplasmic reticulum-associated degradation pathway, responsible for the recognition of misfolded proteins that will be targeted and translocated to the cytosol and degraded by the proteasome. In this study, through a combination of exome sequencing and gene matching, we have identified seven independent families with 11 individuals with bi-allelic protein-truncating variants and one individual with a compound heterozygous missense variant in EDEM3.

A Baseline Measurement of Quality of Life in 322 Adults With Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is characterized by bone fragility and secondary features such as blue sclerae, dentinogenesis imperfecta, hearing loss, ligamentous laxity, and short stature. It was thought that health-related quality of life (QoL) in patients with OI mainly depends on the severity of the skeletal deformities. However, it has become clear that additional factors can affect the QoL in all patients with OI.

Interaction between KDELR2 and HSP47 as a Key Determinant in Osteogenesis Imperfecta Caused by Bi-allelic Variants in KDELR2.

Osteogenesis imperfecta (OI) is characterized primarily by susceptibility to fractures with or without bone deformation. OI is genetically heterogeneous: over 20 genetic causes are recognized. We identified bi-allelic pathogenic KDELR2 variants as a cause of OI in four families.