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.

The Natural History of Dermatosparaxis Ehlers Danlos Syndrome: An Adult Case Series.

Dermatosparaxis Ehlers Danlos syndrome (dEDS) is a very rare monogenic EDS that occurs due to biallelic pathogenic variants in ADAMTS2. Fifteen individuals with dEDS have been reported in the literature, with the oldest being 19 years at follow-up. Given the lack of information regarding adults with dEDS, our aim was to describe adults with dEDS to inform management recommendations in adulthood.

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.

Biallelic occult macular dystrophy.

Purpose: Occult macular dystrophy (OMD) is a cause of visual loss in young adults with a grossly normal fundus appearance. It is considered an autosomal dominant disorder, related to heterozygous pathogenic variants in the gene . The purpose of this study is to report a biallelic form of the disease.

characterization and identification of compound heterozygous variants in H/ACA Ribonucleoprotein Assembly Factor () from Indian population.

Background: H/ACA small nucleolar ribonucleoproteins (snoRNP) form a complex with multiple proteins to accomplish the pseudouridylation of rRNA. The assembly of H/ACA small nucleolar ribonucleoproteins (snoRNP) is initiated by H/ACA ribonucleoprotein Assembly factor, that is, SHQ1. Mutations in have been reported to cause two disorders namely, dystonia-35 childhood onset (OMIM*619921) and neurodevelopmental disorder with seizures and dystonia (OMIM*619922), both of which are inherited in an autosomal recessive manner.

Provincial Review of Adherence to Age-specific Guidelines for Umbilical Hernia Repair and Trends in Management.

Background: Umbilical hernia (UH) is a common pediatric condition, for which delaying surgical repair for asymptomatic UH until after age 3 is recommended due to a high incidence of spontaneous closure. We aimed to determine the adherence to guidelines, rate of urgent surgical repair, outcomes, cost, and interinstitutional referral patterns of UH repair in the province of Quebec (Canada).

Methods: This was a population-based retrospective cohort study of children 28 days to 17 years old who underwent UH repair between 2010 and 2020 using health administrative databases.

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.

Non-oral manifestations in adults with a clinical and molecularly confirmed diagnosis of periodontal Ehlers-Danlos syndrome.

Periodontal Ehlers-Danlos Syndrome (pEDS) is a rare autosomal dominant type of EDS characterised by severe early-onset periodontitis, lack of attached gingiva, pretibial plaques, joint hypermobility and skin hyperextensibility as per the 2017 International EDS Classification. In 2016, deleterious pathogenic heterozygous variants were identified in and , which encode components of the complement system. Individuals with a clinical suspicion of pEDS were clinically and molecularly assessed through the National EDS Service in London and Sheffield and in genetic services in Austria, Sweden and Australia.

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.

Case report and discussion: Pre-implantation genetic diagnosis with surrogacy in vascular Ehlers-Danlos syndrome.

Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal dominant inherited connective tissue condition, characterized by generalized tissue fragility with an increased risk of arterial dissection and hollow organ rupture. In women with vEDS, pregnancy and childbirth carry significant risks of both morbidity and mortality. The Human Fertilisation and Embryology Authority has approved vEDS for pre-implantation genetic diagnosis (PGD), given the potential for life-limiting complications.

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.

The Phenotypic Continuum of -Related Disorders.

Background And Objectives: is associated with a broad spectrum of predominantly neurologic disorders, which continues to expand beyond the initially defined phenotypes of alternating hemiplegia of childhood, rapid-onset dystonia parkinsonism, and cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss syndrome. This phenotypic variability makes it challenging to assess the pathogenicity of an variant found in an undiagnosed patient. We describe the phenotypic features of individuals carrying a pathogenic/likely pathogenic variant and perform a literature review of all variants published thus far in association with human neurologic disease.

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.

AR-V7 exhibits non-canonical mechanisms of nuclear import and chromatin engagement in castrate-resistant prostate cancer.

Expression of the AR splice variant, androgen receptor variant 7 (AR-V7), in prostate cancer is correlated with poor patient survival and resistance to AR targeted therapies and taxanes. Currently, there is no specific inhibitor of AR-V7, while the molecular mechanisms regulating its biological function are not well elucidated. Here, we report that AR-V7 has unique biological features that functionally differentiate it from canonical AR-fl or from the second most prevalent variant, AR-v567.

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.

Transcranial Doppler Ultrasonography in Children With Acute Liver Failure and Severe Hepatic Encephalopathy.

Objectives: To report our single-center use of transcranial Doppler (TCD) for noninvasive neuromonitoring in pediatric patients with acute liver failure (ALF).

Design: Retrospective cohort from January 2016 to June 2019.

Setting: PICU in Bicêtre Hospital, Assistance Publique- Hôpitaux de Paris (AP-HP), a national referral center for pediatric liver transplantation.

Security of medical images for telemedicine: a systematic review.

Recently, there has been a rapid growth in the utilization of medical images in telemedicine applications. The authors in this paper presented a detailed discussion of different types of medical images and the attacks that may affect medical image transmission. This survey paper summarizes existing medical data security approaches and the different challenges associated with them.