エーラス・ダンロス症候群

Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD) are complex multisystemic conditions frequently associated with chronic pain. Central Sensitization (CS)-a state of neural amplification and hyperexcitability-is hypothesized to be a unifying mechanism underlying the heterogeneous symptoms in chronic pain patients. Our aim was to investigate the association between central sensitization and multisystemic symptom burden in patients with hEDS/HSD while identifying independent clinical predictors of CS. We prospectively enrolled 150 adults diagnosed with hEDS/HSD at a specialized joint hypermobility clinic. Participants were evaluated using the Central Sensitization Inventory (CSI) and the SPIDER questionnaire. Clinical CS was defined as a CSI score > 40. Statistical analyses included univariate correlations and multivariable logistic regression. Centrally sensitized patients (n = 76) were significantly younger and predominantly female compared to the non-CS group. While CSI scores correlated strongly with all eight SPIDER domains (p < 0.001), a multivariable logistic regression model (AUC 0.98) identified only three independent predictors of CS: fatigue (OR 1.089), pain (OR 1.067), and cardiac dysautonomia (OR 1.057). Central sensitization in hEDS/HSD is independently associated with a triad of fatigue, pain, and cardiac dysautonomia. Clinical management should shift toward multidisciplinary strategies to effectively address the sensitized state in this population.

BACKGROUND: Energy drinks (EDs) may contain caffeine, amino acids, vitamins, and other ingredients that have been associated with serious adverse effects primarily in children and young adults. OBJECTIVES: We sought to understand ED exposures including demographic trends, clinical effects, and outcomes in the US Poison Centers' National Poison Data System (NPDS) and compared similar reports of caffeinated beverages. METHODS: We analyzed all NPDS closed, human exposures to single-use EDs reported to NPDS between October 1, 2010, and September 30, 2013. RESULTS: NPDS recorded 10,588 cases of ED exposure. Active ingredients were identified in 5,139 (49%) cases. Of the 4,803 (93%) exposures to alcohol-free EDs, 51% were in children 5 years old or younger, 10% were in children 6 to 12 years old, 16% were in adolescents 13 to 19 years old, and 23% were adults at least 20 years old. Unintentional exposures were highest in children 5 years old or younger (75%). Intentional exposures were highest in adolescents (45%). Moderate or major adverse outcomes from EDs containing multiple caffeine ingredients were more common than single ingredient caffeine products (23% vs. 15%; P<0.001). Exposures associated with ethanol EDs had worse outcomes than those without (42% vs. 19%, respectively; P<0.001). The most common clinical effects associated with ED exposures were neurologic (N=1,042, 22%), gastrointestinal (N=792, 17%), and cardiovascular (N=567, 12%); 14 cases were life-threatening, and 1 adolescent girl with vascular Ehlers Danlos syndrome died. Recent follow up from January 1, 2020 to December 31, 2021 shows consistent trends in use and a clear difference between EDs and caffeinated beverage case numbers and medical outcomes. The number of cases was similar in each year except for a notable increase mid-2020 believed related to the pandemic with our query returning 4,367 reported ED cases between 2020 and 2021. CONCLUSION: A substantial proportion of ED calls to poison centers involve children, some of whom experience severe neurologic and cardiac toxicity, among other symptoms. ED exposure calls are more common and have more medical severity than exposures to caffeine or coffee beans alone. The number and severity of adverse ED events warrant efforts to educate the public about the risks, especially in children.

INTRODUCTION: Ehlers-Danlos syndrome (EDS, MIM #606408) is a group of clinically and genetically heterogeneous connective tissue disorders characterized by skin hyperextensibility, joint hypermobility, and tissue fragility. EDS, Classical-like, 1 (clEDS, MIM #606408) is one of the rarest subtypes caused by biallelic pathogenic variants in TNXB (MIM *600985). TNXB haploinsufficiency has been suggested to be associated with EDS, hypermobility type (hEDS; OMIM %130020), which is considered one of the most common EDS subtypes. However, the underlying molecular mechanisms of hEDS remain largely unknown, and heterozygosity for TNXB variants has been proposed as a potential contributing factor rather than a definitive cause. METHODS: We report four siblings from a consanguineous Nusayri family with three siblings affected with clEDS and one sibling with hEDS phenotypes. Whole-exome sequencing and RT-PCR analysis from peripheral blood samples were performed in affected siblings and parents. RESULTS: A homozygous pathogenic TNXB variant (c.3763dup) was identified in three siblings with clEDS. Oldest brother, who met the criteria for hEDS, was heterozygous for this rare variant similar to the parents who were asymptomatic. TNXB expression analysis was significantly lower in homozygous individuals compared to heterozygotes but no significant difference was observed between symptomatic and asymptomatic heterozygotes. CONCLUSION: This is the first detailed clinical report of a Nusayri family in which a homozygous TNXB variant is associated with clEDS, and in which one heterozygous carrier presents with clinical features consistent with hEDS. Our findings contribute to the limited literature on clEDS, particularly in understudied populations. The clinical findings suggest the potential role of TNXB haploinsufficiency in hEDS; however, further research is needed to elucidate the variable expressivity and possible incomplete penetrance associated with hmEDS.

Families living with inherited genetic conditions (IGCs) face practical and emotional challenges that affect individual well-being and family relationships. Although genetic counselling recognises the familial nature of genomic risk, support is often limited to patient-led disclosure. This scoping review examined how family-oriented support is conceptualised, delivered, and evaluated within genetic counselling and related psychosocial services. We define family-oriented support as any practice that explicitly considers relatives and family relationships, and systemic family-oriented care as family-systems-based models treating the family as the unit of care. Following PRISMA-ScR guidance, seven databases were searched to August 2025 for publications describing practices or interventions with a clear family element in services for people living with IGCs. Data were charted descriptively and synthesised using Rolland's Family Systems Illness/Family Systems Genetic Illness (FSI/FSGI) frameworks. Thirty-three publications were included, describing (1) clinical practice with a family element (n = 12), mainly strategies to promote intrafamilial communication, and (2) psychotherapeutic approaches (n = 21), ten of which had been formally evaluated. Qualitative evidence suggested perceived psychosocial benefits, whereas quantitative findings were modest or mixed, constrained by small samples and limited follow-up. Most activity reflected relatively early, proband-centred positions on the FSI/FSGI continuum; only a few multifamily and narrative interventions and one local service model approximated systemic family-oriented care and remained small-scale and specialist. Work focused largely on hereditary breast/ovarian cancer, with marked gaps for untreatable or unpredictable conditions, men, partners, children, and non-Western groups. Advancing systemic, family-level care will require embedding FSI/FSGI principles in training and service design and investing in longitudinal, family-level evaluation.

OBJECTIVE: Open surgical repair continues to be the standard of care for treating thoracic aortic aneurysms (TAA) and Type B Aortic Dissection (TBAD) in patients with connective tissue disorders (CTD). Data on the safety and durability of thoracic endovascular aortic repair (TEVAR) in this patient population remains limited. This study aims to evaluate the perioperative and midterm outcomes of TEVAR in patients with CTD. METHODS: Patients with CTD who underwent TEVAR for TAA or TBAD between 2014 and 2024 were identified in the Vascular Quality Initiative. Patients with ruptured aneurysms, trauma, or those converted to open surgery were excluded. CTD were defined as any documented clinical or genetic history of Marfan syndrome, Loeys-Dietz syndrome, or Ehlers-Danlos syndrome. Patients were stratified and compared by aortic pathology (TAA versus TBAD) and CTD pathology (Marfan syndrome versus Loeys-Dietz/Ehlers-Danlos syndrome). Kaplan-Meier analysis was used to evaluate and compare the midterm event rates of survival, aortic reintervention, aneurysmal degeneration, and dissection propagation. Aneurysmal degeneration was defined as a ≥5 mm increase in aortic diameter from baseline, whereas dissection propagation included antegrade and/or retrograde dissection. RESULTS: 330 patients (median age 50 years [IQR, 35-61]) with CTD underwent TEVAR during the study period, of which 85% (n=281) had Marfan syndrome, 13% (n=42) had Loeys-Dietz syndrome, and 2% (n=7) had Ehlers-Danlos syndrome. TEVAR was performed for TBAD in 63% (n=208) of patients and TAA in 37% (n=122), with 8% (n=25) of procedures performed in an emergent setting. Median hospital stay was 5 days (IQR, 3-9). Perioperative mortality, spinal cord ischemia, and stroke each occurred in 2.1% (n=7) of patients, and reintervention was required in 10.9% (n=36). Patients undergoing TEVAR for TBAD had a longer hospital stay (6 days vs 5 days, p=0.017) and higher perioperative mortality (3.4% vs 0.0%, p=0.039) compared with TAA. Marfan syndrome patients had a significantly lower rate of perioperative mortality (1.4% vs 6.1%, p=0.036) than those with Leoys-Dietz syndrome or Ehlers-Danlos syndrome. At 18-month follow up, overall survival was 88.1% (95% CI, 84.2%-92.0%), with reintervention occurring in 30.8% (95% CI, 23.9%-37.7%), aneurysmal degeneration in 40.2% (95% CI, 29.8%-50.6%), and dissection propagation in 20.4% (95% CI, 10.8%-30.0%). Midterm outcomes were similar between TBAD and TAA for survival (p=0.369), reintervention (p=0.896), aneurysmal degeneration (p=0.151), and dissection propagation (p=0.810). Patients with Marfan syndrome had a higher midterm survival compared to patients with Loeys-Dietz or Ehlers-Danlos syndrome (91.0% vs 71.6%, p=0.001), with no difference observed in reintervention (p=0.190), aneurysmal degeneration (p=0.496), or dissection propagation (p=0.445). CONCLUSION: TEVAR in patients with CTD is associated with acceptable perioperative morbidity and mortality but carries a substantial risk of early and midterm aortic-related complications and reintervention. TEVAR should be used cautiously in this population and primarily reserved for emergency situations or carefully selected patients.