エーラス・ダンロス症候群

Ehlers-Danlos syndrome (EDS) comprises a heterogeneous group of inherited connective tissue disorders. The 2017 International Classification of EDS delineates 13 subtypes, which are caused by pathogenic variants in 19 distinct genes encoding various collagen types or proteins involved in collagen metabolism. EDS is characterized by considerable clinical variability, both across EDS subtypes and in terms of phenotypic polymorphism and disease severity within individual subtypes. The present study describes a clinical case of classical-type Ehlers-Danlos syndrome segregating across three generations, illustrating the clinical variability observed within a single family carrying a single rare pathogenic variant, NM_000093.5(COL5A1):c.4050dup (p.Gly1351fs). Furthermore, this report clarifies and expands the phenotypic spectrum associated with this specific variant.

Maladaptive stress responses may exacerbate chronic widespread pain (CWP) and deserve further investigations. Yet, existing stress induction paradigms lack relevance for individuals with CWP. Patients often report intense stress in response to medical appointments due to the experience of stigma, distrust, and a lack of common understanding about their condition and level of disability. Hence, we developed the Social Benefits Stress Test (SBST), based on the Trier Social Stress Test, replacing the mock job interview, by a fake medical examination where the participant needed to justify their work incapacity. Forty women with CWP due to hypermobile Ehlers-Danlos syndrome or hypermobility spectrum disorders were included. They underwent a 30-min baseline, the SBST and a recovery period. The psychophysiological stress response was captured using self-reported stress ratings, continuous heart rate and electrodermal activity (EDA) monitoring, salivary cortisol and α-amylase levels. Compared to baseline, a significant increase in stress ratings was observed during the SBST, associated with a peak in salivary biomarkers. Heart rate variability analysis showed significant decreases in high frequency power (HF), increases in heart rate, low frequency power (LF) and in LF/HF ratio. EDA analysis revealed significant increases in skin conductance response (SCR). Subjective stress ratings correlated with physiological changes in α-amylase and LF/HF ratio. The SBST induced a reproducible stress response across subjective and physiological measures, validating this task as a relevant experimental model of social stress in chronic pain and a valuable tool for quantitative testing of clinically relevant stress responses in patients with persistent symptoms.

Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder characterised by vascular fragility and risk of arterial complications. Further overlap with autoimmune diseases and multisystem comorbidities creates unique medical management challenges.We present an early 60s female with vEDS suffering from extensive comorbidities including systemic lupus erythematosus, rheumatoid arthritis, fibromuscular dysplasia and more. Over 3 years as our patient, she required multiple surgical interventions (eg, hysterectomy, salpingo-oophorectomy) and multidisciplinary management for chronic pain, autoimmune comorbidities and connective tissue fragility. Unlike more severe presentations commonly reported in vEDS cases, this patient has survived into her 60s and illustrates the spectrum of disease severity.This case highlights the importance of a multidisciplinary approach to complex vEDS, particularly with numerous autoimmune and oncologic comorbidities. While medical decisions must always be carefully individualised, this case illustrates the challenges of coordinating care for an older patient with vEDS and multiple coexisting medical conditions.

BACKGROUND: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder with variable symptom presentation across multiple organ systems and significant morbidity. Little is known about hEDS etiology and identifying patterns of symptom co-occurrence can reveal previously unidentified relationships between phenotypes and inform studies of underlying disease pathophysiology for symptoms that may share functional biological pathways. In this exploratory analysis, we specifically assessed the distribution of symptoms in case and controls to identify clusters of co-occurring symptoms. METHODS: We have interrogated clinically relevant symptom areas in 47 females with hEDS, 36 age-matched female controls and 8 hypermobile patients without chronic pain. Studied symptoms include general health, mental health, body pain, vitality and energy, autonomic symptoms, bleeding, and gastrointestinal symptoms. We conducted hierarchal clustering on principle components (HCPC) to identify groups and compared the groups for the previously described symptoms. Radial plots were used to identify relationships between severe symptom categories. RESULTS: Our analysis reveals statistically significantly more severe symptoms in all categories in people with hEDS compared with age- and sex-matched controls and asymptomatic hypermobile patients. HCPC identified clearly separated Low, Moderate, and High symptom groups within participants. The Low dysfunction groups include nearly all controls and hypermobile patients without chronic pain. The High dysfunction group includes ~60% of people with hEDS, while around 40% are in the Moderate dysfunction cluster. Cluster solutions for all participants were stable with moderate fit (silhouette 0.64; Jaccard boot mean 0.91). Group level radial plots showed high bleeding severity across all symptom clusters, while disproportional severity of general health, physical function, limitation of role due to physical symptoms, pain, and social functioning deficits differentiates the High from Moderate and Low Dysfunction clusters. CONCLUSION: Using this analysis at the group level has revealed patterns suggesting a progression of disease symptoms. People with hypermobility do not uniformly have severe symptoms but instead have some symptoms that differentiate from non-hypermobile individuals. While exploratory, using a radar multi-symptom analysis may be used to evaluate disproportionately severe symptoms contributing to the patterns of global symptom severity. These include pain but also ability to perform roles, suggesting strong utility of physical and occupational therapies to emphasize coping. This may also allow better targeting of etiological studies and may have additional utility at an individual level to develop symptom management strategies.

The Ehlers-Danlos syndromes (EDS) comprise a clinically and genetically heterogeneous group of heritable connective tissue disorders marked by skin hyperextensibility, joint hypermobility, and tissue fragility. Vascular EDS (vEDS) is an autosomal dominant disorder caused by pathogenic variants in COL3A1, the gene encoding type III collagen. The diagnosis of vEDS is confirmed by identifying a pathogenic variant in COL3A1. This systematic review was conducted according to the PRISMA guidelines. Major outcomes included maternal, fetal, and neonatal complications in EDS pregnancies. A comprehensive search was conducted using electronic databases, including PubMed, Cochrane Library, and ScienceDirect, from inception to April 2026. vEDS showed the highest risk profile, with maternal mortality ranging between 0.10% and 50%; however, this wide range is attributed to the inclusion of old studies, in which recent advancements in genetic testing and fetal genotyping were not used. The most common reported obstetric complications were preeclampsia, postpartum hemorrhage, and severe perineal tears. Premature rupture of membranes and preterm premature rupture of membranes were strongly associated with fetal EDS. Preterm birth is the most common complication, ranging between 8.9% and 48.8% of pregnancies across the included studies. Fetal EDS and COL3A1 mutations were more commonly associated with pregnancy complications than the maternal disease itself. Pregnancies complicated by EDS are associated with maternal, fetal, and neonatal complications. vEDS is associated with an increased risk of maternal mortality and a high prevalence of preterm birth. This systematic review underscores the significance of fetal EDS status and COL3A1 variants as a strong predictor of EDS pregnancy complications.