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The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of hereditary disorders of connective tissue, with common features including joint hypermobility, soft and hyperextensible skin, abnormal wound healing and easy bruising. Fourteen different types of EDS are recognized, of which the molecular cause is known for 13 types. These types are caused by variants in 20 different genes, the majority of which encode the fibrillar collagen types I, III and V, modifying or processing enzymes for those proteins, and enzymes that can modify glycosaminoglycan chains of proteoglycans. For the hypermobile type of EDS, the molecular underpinnings remain unknown. As connective tissue is ubiquitously distributed throughout the body, manifestations of the different types of EDS are present, to varying degrees, in virtually every organ system. This can make these disorders particularly challenging to diagnose and manage. Management consists of a care team responsible for surveillance of major and organ-specific complications (for example, arterial aneurysm and dissection), integrated physical medicine and rehabilitation. No specific medical or genetic therapies are available for any type of EDS.

INTRODUCTION: The Ehlers-Danlos syndrome (EDS) is characterized by abnormalities of the connective tissue leading to ligamentous laxity and skin and tissue fragility, bone involvement is an emerging manifestation. We evaluated the bone metabolism, bone mineral density (BMD) and bone quality (measured by trabecular bone score, TBS), and the prevalence of clinical fractures and morphometric vertebral fractures (mVFx) in a large group of adult EDS patients. METHODS: Two-hundred and sixty-six consecutive Caucasian patients, aged ≥18 years (38.3±11.8) (190 females, 76 males) 58% with classical, 34.9% with hypermobility, 4.5% with vascular and 4.8% undefined EDS were enrolled. We had genetic information of 117 patients (74 patients showed no mutations, 2 COL2 mutations, 8 COL3 mutation, 28 COL5 mutations and 5 other genes mutations). In all subjects’ calcium-phosphorous metabolism, bone turnover, BMD at the lumbar spine (LS) and femur (femoral neck, FN and total femur, FT) and radius and TBS by dual-energy X-ray absorptiometry were assessed. Moreover, we evaluated the history of clinical fragility and the mVFx presence by spine radiograph. RESULTS: The 20.6% of patients showed a Z-score BMD ≤-2.0, the 29.8% ≥1 mVFx and the 24.5% ≥1 clinical fractures. Male patients showed a higher prevalence of reduced BMD (31.9 vs 15.6%; p=0.007) and mVFx (41.4% vs 24.8%; p=0.026). Patients with ≥1 mVFx were older (43.2±12 vs 35.6±12; p=0.0001), showed a lower TBS z-score (-1.4±1.7 vs -0.8±1.2; p=0.013) and lower phosphate levels (3.3±0.6 vs 3.5±0.5; p=0.032) with an higher prevalence of hypophosphatemia (24.5% vs 8.8%; p=0.014). No difference was found in prevalence of EDS subtypes or gene mutations. In EDS patients, the VFx presence was significantly associated with TBS and age, even after adjusting for sex and hypophosphatemia. CONCLUSIONS: EDS patients have reduced BMD and bone quality (as measured by TBS) and increased prevalence of clinical and mVFx associated with age and TBS.

The Ehlers-Danlos syndromes (EDS) are a group of heritable, connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. There is phenotypic and genetic variation among the 13 subtypes. The initial genetic findings on EDS were related to alterations in fibrillar collagen, but the elucidation of the molecular basis of many of the subtypes revealed several genes not involved in collagen biosynthesis or structure. However, the genetic basis of the hypermobile type of EDS (hEDS) is still unknown. hEDS is the most common type of EDS and involves generalized joint hypermobility, musculoskeletal manifestations, and mild skin involvement along with the presence of several comorbid conditions. Variability in the spectrum and severity of symptoms and progression of patient phenotype likely depend on age, gender, lifestyle, and expression domains of the EDS genes during development and postnatal life. In this review, we summarize the current molecular, genetic, epidemiologic, and pathogenetic findings related to EDS with a focus on the hypermobile type.

Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and variable tissue fragility. However, there are limited published data on the dental manifestations of EDS. This review systematically assessed the spectrum of published dental anomalies in various types of EDS. Twenty-four individual case reports/series and 3 longer case-control studies, reporting on a total of 84 individuals with a clinical diagnosis of EDS, were included in the data analysis. The main dental features listed in classical EDS were pulp calcification and localized root hypoplasia. Common dental abnormalities observed in vascular EDS were pulp shape modifications (52.2%), exceeding root length (34.8%), and molar root fusion (47.8%). Dentinogenesis imperfecta is a consistent finding in osteogenesis imperfecta/EDS overlap syndrome. Data on dental manifestations in other types of EDS are both rare and generally inconclusive.

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.

The nature of sleep disorders in children with Ehlers-Danlos syndrome (EDS) is unknown. We aimed to describe the type, the management, and the short-term outcome of sleep disorders in children with EDS referred to sleep clinics.This is a retrospective review of medical records and polysomnography tests of children with EDS younger than 18 years who were referred to the sleep clinic. Demographic information and medical history were collected, and polysomnography tests were reviewed. Questionnaires completed during previous clinic visits, including the Pediatrics Sleep Questionnaire (PSQ), Epworth Sleepiness Scale (ESS), and Pediatric Quality of Life Inventory (PedsQL), were also evaluated.Sixty-five patients with EDS-hypermobility type were included. The mean age was 13.15 ± 3.9 years. There were 68% of patients who were female, and 91% of patients were Caucasian. The mean follow-up period was 1.14 ± 1.55 years. Common sleep diagnoses included insomnia (n = 14, 22%), obstructive sleep apnea (OSA) (n = 17, 26%), periodic limb movement disorder (PLMD) (n = 11, 17%), and hypersomnia (n = 10, 15%). In addition, 65% required pharmacologic treatment and 29% were referred to behavioral sleep medicine. For OSA, two patients required continuous positive airway pressure. A significant improvement was observed in the PSQ, ESS, and PedsQL scores during follow-up visits after treatment (n = 34;There is a high prevalence of sleep disorders, including OSA, insomnia, PLMD, and hypersomnia in children with EDS referred to sleep clinics. Specific management can improve quality of life and questionnaire scores of this patient population. Our study emphasizes the importance of screening for sleep disorders in children with EDS.

Hypermobility can be a normal variant in children but it is also found in a group of children presenting with musculoskeletal pain. A smaller group of children will have hypermobility associated with a more concerning syndrome. The clinical challenge is to differentiate those children who have isolated hypermobility with no other associations from those with syndromes that have potentially life limiting complications. In this review we will discuss the assessment of and provide a framework for classifying those children who are found to be hypermobile. We review the components of connective tissue and describe where known the genetic basis for particular phenotypes. In 2017 the international classification of Ehlers Danlos (EDS) was published which supersedes the Villefranche classification. This review describes the diagnostic criteria for the common subtypes of EDS, provides information on further differentials and discusses the management options.

We present an unusual case of leukocytoclastic vasculitis (LCV) demonstrating the Koebner phenomenon. A patient with Ehlers Danlos syndrome had cutaneous lesions exclusively on skin of the lower legs that was traumatized by shaving. Biopsy of the lesions found LCV. Vascular fragility caused by Ehlers Danlos may have contributed to Koebnerization after mild trauma from shaving.

Ehlers-Danlos syndromes (EDS) are a heterogeneous group of inheritable connective tissue disorders characterized by skin hyperextensibility, joint hypermobility and cutaneous fragility with delayed wound healing. Over and above these common features, they differ in the presence or absence of various organ and tissue abnormalities, and differences in genetic causal mechanisms and degree of severity. They are complex and multisystem diseases, with the majority being highly disabling because of major joint problems and neurosensory deficiencies, and in some cases, they may be life-threatening due to associated complications, especially vascular disorders. In 1997, the Villefranche classification defined 6 subtypes of EDS. However, many other new variants have been described over the last years. The "historical" EDS were characterized by abnormalities in fibrillar collagen protein synthesis. More recently, disorders of synthesis and organization of the extracellular matrix have been shown to be responsible for other types of EDS. Thus, many EDS are in fact metabolic diseases related to enzymatic defects. While there is no curative treatment for any type of EDS, early diagnosis is of utmost importance in order to optimize the symptomatic management of patients and to prevent avoidable complications. Patients must be treated and monitored by multidisciplinary teams in highly specialized reference centers. In this article, we present the current state of knowledge on these diseases that continue to be elucidated thanks to new molecular genetic techniques.

Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue disorders, characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Periodontal EDS (pEDS) is a specific EDS subtype caused by heterozygous mutations in complement 1 subunit genes C1R and C1S, with early severe periodontitis as predominant clinical feature. We aimed to systematically assess the spectrum of periodontal abnormalities in all EDS subtypes.An electronic and manual search was conducted in three databases (Medline, LIVIVO, CENTRAL). Publications of all study designs written in English/German without date restriction evaluating periodontal features in EDS were included.Thirty articles on pEDS and thirteen articles on other EDS subtypes were analysed. In pEDS, early severe periodontitis (98.4%) and gingival recession (87.1%) are the predominant features. Reports on periodontal manifestations in other EDS subtypes are rare. Described were severe gingival enlargement in dermatosparaxis EDS, and localized periodontal breakdown related to teeth with shortened roots in classical EDS (n = 3, respectively).Early severe periodontitis is the hallmark of pEDS; there is no evidence that it is part of the clinical phenotype of other EDS subtypes. Stringent analyses of periodontal manifestations in most EDS subtypes are missing. Prospero registration number CRD42017056889.

This paper discusses the perioperative care needs of patients with Ehlers Danlos type IV (vascular) syndrome. Ehlers Danlos syndrome (EDS) is a heritable group of connective tissue disorders characterised by varying degrees of tissue, blood vessel and internal organ fragility as well as skin and joint hypermobility (De Paepe & Malfait 2012). In 1997 EDS was revised and classified into six subtypes: classical (Types I and II), hypermobility, vascular (Type IV), kyphoscoliosis and arthrochalasia type. Each classification has been based on the following aspects: diagnostic uniformity, natural history, management, genetics, and the identification of potential areas for research (Beighton et al 1998). Vascular type EDS has serious implications for any form of surgical procedure and it is therefore imperative that theatre staff are fully conversant with the needs of this patient group. Overall awareness needs to be increased, particularly as most patients will most frequently be seen in an emergency situation, as elective procedures are avoided as far as possible.

Key Clinical Message Ehlers–Danlos syndrome hypermobility type (EDS‐HT) is an underdiagnosed genetic connective tissue disorder that causes joint hypermobility and widespread pain. We present a patient with the chief complaint of shoulder pain, a long history of widespread joint pain, and associated comorbidities. EDS‐HT provided a unifying diagnosis and direction for management.

Key Clinical Message Correctional surgery was performed on a 3‐year‐old intact male shih tzu presenting with Ehlers–Danlos syndrome, ocular disease, and skin fold dermatitis. A one‐year follow‐up showed that no further clinical corrections were needed. Therefore, surgery could be considered in some canine patients with Ehlers–Danlos syndrome.

The Ehlers-Danlos syndromes (EDS) are hereditary disorders that affect the connective tissue and collagen structures in the body. Several types of EDS have been identified. Oral and mandibular structures, which include oral soft tissue, dentition, facial and head pain, and the functioning of the temporomandibular joint (TMJ), are variably affected in the various types of EDS. These various manifestations of EDS have been noted for many years, but newer diagnostic techniques and studies are shedding additional light on the challenges faced by EDS patients in the area of oral and mandibular disorders. Further, the impact of temporomandibular disorder (TMD) on musculoskeletal dysfunction and vice versa, make this an important feature to recognize. Oral and mandibular hypermobility of the TMJ with associated consequences of EDS are noted. These features, diagnostic parameters and treatment procedures are presented. © 2017 Wiley Periodicals, Inc.

The role of orthopedic surgery in Ehlers-Danlos syndrome is inherently controversial, opaque to most patients and many medical providers, and difficult to discern from available medical literature. Non-operative treatment is preferable, but for carefully selected patients, specific joint stabilization and nerve decompression procedures can provide symptomatic relief when conservative measures fail. © 2017 Wiley Periodicals, Inc.

These recommendations relate to patients who, despite their number, are rarely diagnosed or after a painful and dangerous medical wandering of 20 years on average.

Ehlers-Danlos disease, despite its frequency, remains largely unheard of and is almost never diagnosed. Thus, Professor Rodney Grahame [1] of the London University says..

Ghali and colleagues give an overview of Ehlers-Danlos syndromes (EDS) and their increasing public awareness owing to the growing number of EDS patient organisations.1 Joint hypermobility is the cardinal characteristic of EDS. Spontaneous dislocation of temporomandibular joints might be one of the first symptoms that patients with EDS present with. Patients with EDS are frequent attenders in …

Drug-induced skin reactions are common, but only a small portion (10%) are attributed to a vasculitic mechanism. Small-vessel vasculitis (SVV) with leukocytoclastic histopathology is usually described in drug-induced vasculitis; however, given the shared histopathologic features between drug-induced vasculitis and other SVV, it is crucial to rule out infectious or other autoimmune etiologies underlying the clinical presentation. We hereby sought to present a case of sulfonamide-induced leukocytoclastic vasculitis, limited to the skin, in a patient with Ehlers-Danlos syndrome in order to emphasize the need for a broad diagnostic and clinical exclusion workup.

Difficult airway management is one of the most challenging situations for an anesthesiologist. If not handled properly, it can lead to severe complications, even death. Video-laryngoscopy (VL) is one of the many techniques developed for this purpose. Ehlers-Danlos Syndrome (EDS) is a rare disease requiring possible difficult airway management due to temporo-mandibular dysfunction or occipito-atlanto-axial instability. We herein present two pediatric EDS cases who required surgery. The first case was a 9-year-old, male, ASA II EDS patient scheduled for strabismus surgery, and the second case was a 12-year-old, male, ASA III EDS patient who was also diagnosed with a brain cyst and lymphoma, due for emergency surgery for acute abdomen. With their heads in a neutral position, both patients were intubated without tissue trauma at first attempt using video-laryngoscopy. No complications were encountered in both cases. We believe that using video-laryngoscopy for managing difficult pediatric airways may be beneficial in avoiding complications., Zor hava yolu yönetimi, anestezist için en problemli durumlardan biridir ve komplikasyonlara, hatta ölüme neden olabilir. Videolaringoskop, bu sebeple geliştirilen tekniklerden birisidir. Ehlers-Danlos Sendromu, temporomandibular disfonksiyon veya oksipito-atlanto-aksiyel instabilite nedeniyle zor hava yolu yönetimine ihtiyaç duyulabilen nadir bir hastalıktır. Burada Ehlers-Danlos Sendromu (EDS) tanılı iki olgu sunulmuştur. İlk olgu, 12 yaşında, ASA II, EDS tanılı, strabismus nedeniyle cerrahi planlanan erkek hasta, ikinci olgu ise 9 yaşında, ASA III, EDS, beyin kisti ve lenfoma tanılı, akut batın sebebiyle acil cerrahiye ihtiyacı doğan erkek hastadır. Her iki hasta, başları nötral pozisyondayken, dokuyu travmatize etmeden, video-laringoskop ile ilk denemede entübe edilmiştir ve herhangi bir komplikasyonla karşılaşılmamıştır. Olası komplikasyonlardan kaçınmak için pediatrik zor hava yolu yönetiminde video-laringoskop kullanımının faydalı olacağını düşünüyoruz.

The Ehlers-Danlos syndromes (EDS) and associated hypermobility spectrum disorders (HSD) are a heterogenous group of connective tissue disorders associated with significant morbidity. The urogenital aspects of these disorders are understudied and there is little guidance on the prevalence, types, or outcomes of urogenital complications in EDS/HSD. Our objective was to perform a scoping review to characterize and synthesize the literature reporting urogenital and pelvic complications in EDS/HSD patients. We performed a systematic search of three databases (Medline, CINAHL, Embase) to January 2019. English language, full-text articles reporting on urogenital or pelvic complications in EDS/HSD were included. A total of 105 studies were included (62 case reports/series, 43 observational) involving patients with hypermobile (23%), vascular (20%), classical (12%) EDS, and HSD (24%). Some studies looked at multiple subtypes (11%) or did not report subtype (33%). Reported complications included urinary (41%), gynecological (36%), obstetrical (25%), renal (9%), and men's health problems (7%), with some studies reporting on multiple areas. Urinary and gynecological complications were most prevalent in patients with HSD, while a broad range of complications were reported in EDS. While further research is required, results suggest a higher index of suspicion for urogenital problems is probably warranted in this population.

Background: The European Reference Network for rare and complex connective tissue and musculoskeletal diseases (ERN ReCONNET) is a European network of 26 healthcare providers (HCPs), that aims at developing a comprehensive and harmonized approach to 10 rare and complex connective and musculoskeletal diseases (rCTDs). The network gathers the community of health care professionals and patients’ representatives. The involvement of patients is structured thanks to the creation of the European Patient Advocacy Groups (ePAG). 3 ePAGs representing each disease pillar are members of the steering committee. The Ehlers-Danlos Syndromes (EDS) are represented in the ERN ReCONNET with the exception of vascular EDS represented in the VASCERN ERN. Objectives: To raise awareness on the unmet needs related to EDS in the EU through attracting and engaging more experts, specialists and HCPs in order to address those needs. Methods: At present, the EDS is represented by 2 HCPs and 2 official ePAGs, senior and junior disease coordinators have been identified both among HCPs and ePAG, in particular the EDS ePAGs intensively sought for unmet needs of EDS into their wider European Community. All needs identified by ePAGs were discussed with the senior and junior coordinators and their contribution was added in a dedicated paragraph of the article, acknowledging them as co-authors. Among other activities, a state of the art on clinical practice guidelines (CPGs) has been performed also for EDS1, in which patients and clinicians highlighted the most important unmet needs. Results: As the new 2017 International EDS nosology2 was only published in March 2017, EDS still lack Clinical Practice Guidelines and recommendations. The main EDS unmet needs identified concern the need to develop data on prevalence and clinical features, the identification of reliable biomarkers and the implementation of advanced instrumental imaging techniques. The management of pain, fatigue and psychological support have also been identified as a major topic to be addressed. More efforts should be put also on the education of healthcare professionals in order to provide faster diagnosis and better care to EDS patients. A stronger representation of EDS centres of expertise in the ERNs is needed, especially considering the crucial added value represented by the possibility of discussing clinical cases in the Clinical Patient Management System provided by the European Commission. Conclusion: The ERN offers a real opportunity to develop better standards of care taking into account patients unmet needs. It is critical to increase EDS awareness and to attract HCPs for the follow-up and care of patients to be able to meet the unmet needs of the EDS patient population and healthcare professionals. Acknowledgement: : on behalf of the ERN ReCONNET European Patients Advocacy Group Disclosure of Interests: None declared

Background In 2017, a new international classification for Ehlers-Danlos syndromes (EDS) was published following a consensus meeting in New York, USA. The new criteria for hypermobile EDS (hEDS) are more specific compared to previously termed EDS-hypermobility type (EDS-HT). They include the presence of hypermobile joints (Beighton score ≥6),≥5 of 12 physical features, a first-degree family member independently meeting criteria, and the presence of musculoskeletal pain or dysfunction, in the absence of other diagnoses. The criteria have not been formally validated in a paediatric population. Aim To evaluate the hEDS diagnostic criteria in a single UK tertiary paediatric rheumatology centre. Methods We retrospectively analysed the electronic records of patients seen in clinic between April 2017 and April 2018. Patients were included if the referral letter described joint pain, hypermobility, joint subluxation/dislocation or suspected EDS. Results Seventy three patients met the inclusion criteria with ages ranging from 19 months to 16 years old. Three (4.1%) children met criteria for hEDS. 57 (78%) were diagnosed with symptomatic hypermobility. 4 (5.4%) with biomechanical pain not hypermobile, nine (12%) were asymptomatic and normal for age and one was referred to genetics for suspected Loey-Dietz. All symptomatic patients received explanation for symptoms and those confirmed as hypermobile received an information leaflet. 54 (74%) children were referred to physiotherapy. 14 (19%) to occupational therapy, 12 (16%) received exercise education in clinic, and 7 (10%) received reassurance alone. 4 (5%) were referred to psychology for chronic pain management. All patients meeting hEDS criteria were referred to a geneticist and received multidisciplinary team (MDT) input. 53 (73%) children were discharged following initial appointment. Conclusion The aim of the hEDS diagnostic criteria is to identify a uniform phenotypic group for further research. Our study demonstrates that majority of children presenting with hypermobility and musculoskeletal pain do not meet the criteria. Exclusion of all heritable connective tissue disease is important clinically and provides reassurance to families. The child’s difficulties should then be the sole focus of management with promotion of increased functioning and pain management.

Myodural bridges have been described in various species as connective tissue structures “bridging” small cranio-cervical muscles to the dura. Myodural bridges are thought to stabilize the dural sac during head and neck movements and promote cerebrospinal fluid motion; however, their role in neurological diseases has not yet been established. We report ultrasonographic visualization, necropsy, histopathologic and ultrastructural findings of myodural bridges in horses with hereditary equine regional dermal asthenia (HERDA), an equine model of Ehlers-Danlos syndromes. Five HERDA and 5 control horses were studied. Post-mortem examination and ultrasonographic studies (3 HERDA and 4 controls) demonstrated that the atlanto-occipital and atlanto-axial myodural bridges are dynamic structures “moving” the dura. En block resection of the myodural bridges (4 HERDA and 5 controls) was accomplished and histopathology showed myofiber degeneration in 3 HERDA horses and 1 control. Ultrastructural examination revealed loosely packed collagen fibrils with abnormal orientation in all HERDA horses compared to mild abnormalities in 2 controls. Our study provides necropsy and ultrasonographic evidence of the dynamic aspect of the myodural bridges as dural sac stabilizers. Myodural bridges may be pathologically altered in connective tissue disease as evidenced by the ultrastructural morphology in the HERDA myodural bridge.

Considerable interest has arisen concerning the relationship between hereditary connective tissue disorders such as the Ehlers-Danlos syndromes (EDS)/hypermobility spectrum disorders (HSD) and autism, both in terms of their comorbidity as well as co-occurrence within the same families. This paper reviews our current state of knowledge, as well as highlighting unanswered questions concerning this remarkable patient group, which we hope will attract further scientific interest in coming years. In particular, patients themselves are demanding more research into this growing area of interest, although science has been slow to answer that call. Here, we address the overlap between these two spectrum conditions, including neurobehavioral, psychiatric, and neurological commonalities, shared peripheral neuropathies and neuropathologies, and similar autonomic and immune dysregulation. Together, these data highlight the potential relatedness of these two conditions and suggest that EDS/HSD may represent a subtype of autism.

Resume La maladie d’Ehlers-Danlos reste une pathologie peu connue avec souvent un retard diagnostique important. La scoliose est un des symptomes inconstants du SED mais tous les auteurs reconnaissent le SED comme une etiologie des scolioses. Il faut donc pouvoir evoquer le diagnostic de SED devant une scoliose atypique. Cependant, tres peu de references existent sur la scoliose et le SED dans la litterature.

Ehlers-Danlos Syndrome (EDS) is a connective tissue disease with heterogeneous subgroups. In type IV EDS, also known as vascular EDS (VEDS), the underlying genetic anomaly consists of a mutation of the COL3A1 gene encoding the type III procollagen. As a result of the mutation, pathological findings due to excessive brittleness of the tubular organs or vessels occur. In our case, we present a patient with sudden death due to colon perforation which was diagnosed with EDS type IV after further examination in the autopsy. Forensic medicine experts should consider the possibility of EDS type IV after the detection of spontaneous ruptures in the internal organs during the autopsy. We think that it would be appropriate to report this autosomal dominant and potentially fatal condition to family members.

Introduction Ehlers-Danlos syndrome (EDS) is an heritable collagen disorder with various multisystemic clinical manifestations affecting primarily skin, ligaments and joints, blood vessels and internal organs. The clinical spectrum is very large from mild skin and joint hypermobility to severe physical disability. Patients with Ehlers-Danlos syndrome often complain of poor sleep quality and fatigue with impaired quality of life. The purpose of this study was to assess any objective sleep disturbances in EDS by polysomnography. Methods In this case-control study, we included 47 patients EDS type III (hypermobile type) (29 F et 18 M) which were one to one strictly matched to 47(29 F et 18 M) controls according to sex, age, and BMI. Participants underwent level-1 polysomnography for a complete sleep study. Results The two group were strictly similar for age and BMI (mean age 29.3 ± 9.2 years, BMI 23.3 ± 4.4 kg/m²). Total Sleep time (TST) was significantly reduced in EDS (343.7 ± 69.3 min versus 395 ± 74.8 min; F= 11.9; p< 0.01). Sleep quality was significantly impaired, with a decreased Sleep efficiency (SE): 74.4 ± 10.5 versus 90.2 ± 7.8 F= 68.5; p< 0.001), an increased wake after sleep onset (WASO) time (116.5 ± 45.7 min versus 43.3 ± 36.8 min; F= 73.2; p 10/hour) was 75% versus 7.1 % in the control group (OR 5.1 (95% CI 2.3 to 14.7); p Conclusion PSG may help in better understanding the diagnosis and treatments of EDS patients. Support

Familial thoracic aortic aneurysm syndrome (FTAAS) is a heterogenous group of disorders characterized by vascular connective tissue disease (CTD) resulting in aortopathy. We describe a new mutation in PLOD1 (c.534C>A (p.Ser178Arg)), a gene known to cause non-vascular kyphoscoliotic Ehlers Danlos

ObjectiveTo report the effort of the European Reference Network for Rare and Complex CONnective tissue and musculoskeletal diseases NETwork working group on Ehlers-Danlos syndromes (EDS) and related disorders to assess current available clinical practice guidelines (CPGs) specifically addressed to EDS, in order to identify potential clinician and patient unmet needs.MethodsSystematic literature search in PUBMED and EMBASE based on controlled terms (MeSH and Emtree) and keywords of the disease and publication type (CPGs). All the published articles were revised in order to identify existing CPGs on diagnosis, monitoring and treatment of EDS.ResultsLiterature revision detected the absence of papers reporting good quality CPGs to optimise EDS patient care. The current evidence-based literature regarding clinical guidelines for the EDS was limited in size and quality, and there is insufficient research exploring the clinical features and interventions, and clinical decision-making are currently based on theoretical and limited research evidences.ConclusionsMany clinician and patient unmet needs have been identified.

Introduction Ehlers Danlos syndrome is a group of inherited heterogenous multisystem disorders characterised by skin hyperextensibility, atrophic scarring, joint hypermobility and generalised tissue fragility. Hypermobile EDS (hEDS)is the most common type. Marfan syndrome(MS) is also a multisystem disorder caused by a mutation in FBN1 gene which shares some phenotypic features with Hypermobile EDS such as joint hypermobility. Recent studies have suggested an association of Functional Gastrointestinal Disorders with joint hypermobility. Methods Data was collected from 27 MS patients (10 male and 17 females, age range 19–35 years mean 27) and 33 hEDS patients (3 male and 30 females, age range 19–32 years mean 23) with no organic gastrointestinal diagnosis, using SF36 RAND and Rome IV Diagnostic questionnaire and compared to control group (200 respondents,92 male and 108 female; age range 18–84, mean 42.4) to assess the burden of GI symptoms in these patients. Data analysis was carried out using Microsoft Excel and SPSS version 25 (IBM Corporation, America). Results In both groups the majority (78.3%) of respondents were female within the age range of 19–35 years. Both groups of patients showed a higher prevalence of abdominal symptoms as compared to the control group, however the hEDS group not only showed a higher prevalence but more frequent and severe symptoms meeting Rome IV criteria for diagnosis of FGIDs. 16 (49%)of the EDS patients met the criteria for more than one FGID. p values were significant (p The hEDS group also scored lower on quality of life scores(QOL) in comparison to either of the other groups with a mean score of 48.6 (95%CI 25.3–33.4,p Conclusions FGIDs are reported in both Marfan syndrome and Hypermobile Ehlers Danlos syndrome but appear to be more common and severe in hEDS. These patients score lower on quality of life scores as well despite hypermobility being a common feature of both conditions. Further research is needed in this area to see whether there are other factors that can explain this difference.

Introduction The Ehlers-Danlos Syndrome (EDS) can presentis a reduction in fibroblast proliferation and collagen production. Microneedling a minimally invasive technique that through mechanical stimulus there is incentive to the production of collagen and elastin. Objective Present a case study in a patient with EDS complaining of flaccidity on large genital labia, using microneedling as a therapeutic proposal. Methodology A 36-year-old female with EDS type III. The external genitalia showed tissue flaccidity associated with hyperchromia. Microneedling was performed with 0.5 mm needles and the cosmetology was used soon after the application. The level of pain was questioned to the patient through a Likert scale. The clinical response to treatment was evaluated through self-report, visual analogue scale and analysis of photographic images. Five other people evaluated the results through before and after images. Results Microneedle was shown to be bearable in relation to pain and associated with cosmetology for tissue flaccidity due to EDS in the genital region proved to be very satisfactory for the patient, as well individuals who evaluated the comparative image. Conclusion Microneedle associated with cosmetology may be a new option for studies on skin flaccidity treatments on individuals with EDS and for treatments of genital hyperchromias.

The authors report a rare case of recurrent tethered cord syndrome in the context of Ehlers Danlos Syndrome and mosaic trisomy chromosome 20 that was successfully treated by shortening vertebral column with a partial corpectomy. The patient was a 20-year-old female diagnosed with Ehlers Danlos type 3 and mosaic trisomy 20.Her lower extremities sensation and strength gradually deteriorated, and a clinical and radiographic diagnosis of tethered cord syndrome was made. She underwent three detethering surgeries, which all were complicated with retethering and arachnoid cyst formation. The massive amount of scar formation found on the third attempt at detethering surgery forced the surgeon to leave the spinal cord tethered and plan for spinal-shortening osteotomy. A T11 vertebral column resection shortened the spine by 20 mm and allowed gradual and significant recovery of lower limb neurological deficits. Authors reported this rare case in order to (a) propose the consideration of the spine-shortening osteotomy as the primary surgery in a tethered cord syndrome patient with a higher possibility of scar formation like Ehlers Danlos Syndrome (b) and to report a rare case of tethered cord syndrome in the context of Ehlers Danlos Syndrome with mosaic trisomy 20 and (c) raise the awareness of the possibility of unreported genetic association of Ehlers Danlos Syndrome with mosaic trisomy 20.

The Ehlers-Danlos syndromes (EDS) comprise a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs), characterised by joint hypermobility, hyperextensibility of the skin and tissue fragility that can induce symptoms from multiple organ systems. The latest EDS nosology distinguished thirteen subtypes with an overlap of phenotypic features, making the clinical diagnosis rather difficult and highlighting the importance of molecular diagnostic confirmation. Although the nervous system is not considered a primary target of the underlying molecular defect, recently, increasing attention has been focused on neurological manifestations of EDS. Among them, epilepsy represents a frequent cause of morbidity in these syndromes and can influence the long-term evolution of these patients, but the mechanisms are needed to be clarified. The aim of this review is to give a comprehensive overview and to analyze a possible association between EDS and epilepsy, focusing on the various brain anomalies and the types of epilepsy reported in patients affected by EDS.

Andrew R. Brodbelt & Graham Flint (2017): Ehlers Danlos, Complex Chiari and cranio-cervical fixation: how best should we treat patients with hypermobility? British Journal of Neurosurgery. DOI: 10....