Chronic Pain and Joint Hypermobility: A Brief Diagnostic Review for Clinicians and the Potential Application of Infrared Thermography in Screening Hypermobile Inflamed Joints.

Joint hypermobility syndromes, particularly chronic pain associated with this condition, including Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD), present diagnostic challenges due to their multifactorial origins and remain poorly understood from biomechanical and genomic-molecular perspectives. Recent diagnostic guidelines have differentiated hEDS, HSD, and benign joint hypermobility, providing a more objective diagnostic framework. However, incorrect diagnoses and underdiagnoses persist, leading to prolonged journeys for affected individuals. Musculoskeletal manifestations, chronic pain, dysautonomia, and gastrointestinal symptoms illustrate the multifactorial impact of these conditions, affecting both the physical and emotional well-being of affected individuals. Infrared thermography (IRT) emerges as a promising tool for joint assessment, especially in detecting inflammatory processes. Thermal distribution patterns offer valuable insights into joint dysfunctions, although the direct correlation between pain and inflammation remains challenging. The prevalence of neuropathies among hypermobile individuals accentuates the discordance between pain perception and thermographic findings, further complicating diagnosis and management. Despite its potential, the clinical integration of IRT faces challenges, with conflicting evidence hindering its adoption. However, studies demonstrate objective temperature disparities between healthy and diseased joints, especially under dynamic thermography, suggesting its potential utility in clinical practice. Future research focused on refining diagnostic criteria and elucidating the underlying mechanisms of hypermobility syndromes will be essential to improve diagnostic accuracy and enhance patient care in this complex and multidimensional context.

Joint Hypermobility Syndrome and Membrane Proteins: A Comprehensive Review.

Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Asymptomatic EDSs, joint hypermobility without associated syndromes, EDSs, and hypermobility spectrum disorders are the commonest phenotypes associated with joint hypermobility. Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. JHS can be a sign of a more serious underlying genetic condition, such as EDS, which affects the cartilage, bone, fat, and blood. The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. Membrane proteins are a class of proteins embedded in the cell membrane and play a crucial role in cell signaling, transport, and adhesion. Dysregulated membrane proteins have been implicated in a variety of diseases, including cancer, cardiovascular disease, and neurological disorders; recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. This article presents an exploration of the causative factors contributing to musculoskeletal pain in individuals with hypermobility, based on research findings. It aims to provide an understanding of JHS and its association with membrane proteins, addressing the clinical manifestations, pathogenesis, diagnosis, and management of JHS.

Unraveling the genetic collagen connection: clinical and therapeutic insights on genetic connective tissue disorders.

Hereditary connective tissue disorders include more than 200 conditions affecting different organs and tissues, compromising the biological role of the extracellular matrix through interference in the synthesis, development, or secretion of collagen and/or its associated proteins. The clinical phenotype includes multiple signs and symptoms, usually nonspecific but of interest to rheumatologists because of musculoskeletal involvement. The patient´s journey to diagnosis is long, and physicians should include these disorders in their differential diagnoses of diseases with systemic involvement. In this review, insights for the diagnosis and treatment of osteogenesis imperfecta, hypermobility spectrum disorder/Ehlers-Danlos syndrome, Marfan, Loeys-Dietz, and Stickler syndromes are presented.

Case report: A novel COL3A1 variant in a Colombian patient with isolated cerebrovascular involvement in vascular Ehlers-Danlos syndrome.

Introduction: To date, approximately 600 unique pathogenic variants have been reported in COL3A1 associated with vascular Ehlers-Danlos syndrome (vEDS). The objective of this study was to describe a patient with a novel variant in COL3A1 associated with vEDS. Case report: We describe the clinical history and thorough phenotyping of a patient with brain aneurysms and identified a novel pathogenic variant in COL3A1. This male patient reported transient focal neurologic symptoms. Physical examination showed abnormal atrophic scarring, horizontal stretch marks under the arms, and an acrogeric appearance of the skin of the hands and feet. Brain imaging revealed extensive dilation of both internal carotids and the vertebrobasilar system. Molecular analysis identified a variant in COL3A1 (NM_000090.4):c.3058G>T p.(Gly1020Cys), which was classified as likely pathogenic. Currently, the patient has never had an event concerning dissection/rupture of tissues that could be affected in this condition. Conclusion: This report demonstrates that exhaustive evaluation with clinical and genetic approaches should be considered in patients with vascular abnormalities. vEDS has a variable clinical presentation and often goes unrecognized, even though it is related to life-threatening complications and a shortened life expectancy. Diagnosis confirmed by genetic testing is crucial to determining appropriate surveillance, prevention, treatment, and genetic counseling.

Generalized Joint Hypermobility: A Statistical Analysis Identifies Non-Axial Involvement in Most Cases.

CONTEXT: Joint hypermobility (JH) represents the extreme of the normal range of motion or a condition for a group of genetically determined connective tissue disorders. Generalized joint hypermobility (GJH) is suspected when present in all four limbs and the axial skeleton, scored in prepubescent children and adolescents by a Beighton Score (BS) ≥ 6. Parameters are also used to identify GJH in hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSDs). The purpose of this study is to characterize children with JH based on the location of variables in the BS ≥ 6 and identify children with JH in the axial skeleton, upper limbs (ULs), and lower limbs (LLs) simultaneously. METHODS: We analyzed 124 medical records of one- to nine-year-old children with JH by BS. RESULTS: The characterization of GJH by combinations of the axial skeleton, ULs, and LLs simultaneously totaled 25.7%. BS = 6 and BS = 8 consisted of variables located in ULs and LLs. BS = 7 included the axial skeleton, ULs, and LLs. BS ≥ 6 represents the majority of the sample and predominantly girls. CONCLUSIONS: BS ≥ 6 represents the majority of the sample and predominantly girls. Most characterized children with GJH present BS = 6 and BS = 8 with variables located only in ULs and LLs, a condition that does not imply the feature is generalized. In children, BS = 7 and BS = 9 characterize GJH by including the axial skeleton, ULs, and LLs. These results draw attention to the implications for defining the diagnosis of hEDS and HSDs.

Manejo odontológico de pacientes con el síndrome de Ehlers-Danlos. Revisión narrativa / Dental management in patients with Ehlers-Danlos syndrome. Narrative review

Resumen El síndrome de Ehlers-Danlos es una enfermedad hereditaria, producida por mutaciones cromosómicas que pueden llegar a tener un comportamiento autosómico dominante, recesivo o ligado al cromosoma X. Se caracteriza por defectos en las enzimas encargadas de la estructura y síntesis de colágeno. En vista de los 20 tipos de colágeno que existen, este síndrome es extremadamente heterogéneo tanto en su presentación clínica como en su progresión y evolución. Dentro de los signos y síntomas habituales encontramos la hiperlaxitud articular, hiperelasticidad de la piel e hiperequimosis de los vasos sanguíneos. Con relación a las complicaciones que pueden presentar estos pacientes, encontramos dislocaciones articulares, fragilidad en la piel, dolor articular, ruptura de grandes vasos sanguíneos, dificultad en la cicatrización y, en consecuencia, mayor incidencia de procesos infecciosos y de cicatrices poco estéticas. Presenta una incidencia de 1 caso cada 2.500-5.000 nacidos vivos. Por ello, es fundamental que el odontólogo se encuentre familiarizado con el manejo médico-dental de estos pacientes, a fin de estar preparado para brindarles un tratamiento adecuado y responder ante las posibles complicaciones que se pueden presentar. En esta revisión se emplearon resultados extraídos manualmente de artículos, indexados en las bases de datos PUBMED y EBSCO, que respondían a la búsqueda de los términos Ehlers-Danlos syndrome, dental management y oral surgery. El objetivo fue describir el manejo médico-odontológico del paciente con síndrome de Ehlers-Danlos hasta la fecha.

Abstract Ehlers-Danlos syndrome is a hereditary disease, produced by chromosomal mutations that can have an autosomal behavior, which can be dominant, recessive or X-linked. It is characterized by defects in the enzymes responsible for the structure and synthesis of collagen. In view of the 20 existent types of collagen, this syndrome is extremely heterogeneous in its clinical presentation, as well as in its progression and evolution. Within the usual signs and symptoms, we find joint hyperlaxity, skin hyperelasticity and hyper-ecchymosis of the blood vessels. Regarding the complications that these patients can present, we find joint dislocations, skin fragility, joint pain, rupture of large blood vessels, difficulty in healing and, consequently, a higher incidence of infectious processes and unsightly scars. It presents an incidence of 1 case every 2.500-5.000 live births. Therefore, it is essential that the dentist is familiar with the medical-dental management of these patients, in order to be prepared to provide them with adequate treatment and respond to possible complications that may arise. In this review, results were manually extracted from articles, indexed in the PUBMED and EBSCO databases, that respond to the search for the terms Ehlers-Danlos syndrome, dental management and oral surgery. The aim was describing the medical-dental management of patients with Ehlers-Danlos syndrome to date.

Growing skull fracture in a child with Ehlers-Danlos syndrome: case report and literature review.

INTRODUCTION: Growing skull fracture (GSF) is a rare complication of head trauma in the pediatric population, commonly observed in children younger than 3 years. DISCUSSION: In this report, the authors describe a case of a 3-year-old male child, with clinical features of Ehlers-Danlos syndrome (EDS), who developed a GSF in frontal bone after a crib fall, treated with duraplasty and cranioplasty with autologous craft. Here, pertinent literature was reviewed with an emphasis on surgical techniques, and correlation with the mentioned syndrome. CONCLUSION: This is the first case of GSF in association with EDS in the literature. The relevance of the case described concerns the rarity of the condition itself, the atypical presentation, and the intraoperative findings, which showed the important fragility of the dura mater, probably due to EDS. Therefore, this syndrome, besides having influenced the pathogenesis, was also a challenging factor in the surgical treatment.

Ictiosis vulgar asociada a síndrome de Ehlers Danlos tipo clásico en una niña / Ichthyosis Vulgaris Associated with Ehlers Danlos Syndrome Classic Type in a Girl

Introducción: La ictiosis vulgar y el síndrome de Ehlers Danlos tipo clásico integran dos genodermatosis que presentan en común un patrón de herencia autosómico dominante, pero muestran manifestaciones clínicas variadas. Es infrecuente encontrar concomitancia de ambas dermatosis en un mismo paciente, y cuando ocurre la heterogeneidad clínica hace complejo el diagnóstico. Objetivo: Exponer un caso que presentó ictiosis vulgar asociada con el síndrome de Ehlers Danlos tipo clásico, en el que el análisis del árbol genealógico contribuyó a orientar el diagnóstico. Presentación del caso: Paciente femenina de 10 años de edad, atendida en la consulta especializada de genodermatosis en Las Tunas. Presentaba, desde edades tempranas, lesiones escamosas localizadas en las piernas y brazos, y que empeoraban durante el invierno. Desde los nueve años comenzó a mostrar luxaciones frecuentes de hombro derecho e hiperextensibilidad de la piel. Constaban antecedentes familiares de piel escamosa en miembros de la familia materna e hipermovilidad articular en varios miembros de la familia paterna: El árbol genealógico contribuyó a orientar el diagnóstico y a realizar la atención médica adecuada. Conclusiones: Se trató un caso interesante porque resulta infrecuente encontrar en un mismo paciente dos enfermedades genéticas, lo cual implicó dificultades en el momento de confirmar el diagnóstico, así como su atención. A este diagnóstico, en el caso de ambas genodermatosis, contribuyó el análisis del árbol genealógico familiar, herramienta fundamental en la determinación de enfermedades genéticas(AU)

Introduction: Ichthyosis vulgaris and Ehlers Danlos syndrome classic type comprise two genodermatoses that share an autosomal dominant pattern of inheritance, but show varied clinical manifestations. It is rare to find concomitance of both dermatoses in the same patient, and when this occurs the clinical heterogeneity makes the diagnosis complex. Objective: To present a case of ichthyosis vulgaris associated with classic Ehlers Danlos syndrome, in which analysis of the family tree helped to guide the diagnosis. Case presentation: 10-year-old female patient seen at the specialised genodermatosis clinic in Las Tunas. She presented, from an early age, with scaly lesions located on the legs and arms, which worsened during the winter. From the age of nine he began to show frequent dislocations of the right shoulder and hyperextensibility of the skin. There was a family history of scaly skin in members of the maternal family and joint hypermobility in several members of the paternal family: the family tree helped to guide the diagnosis and appropriate medical care. Conclusions: This was an interesting case because it is rare to find two genetic diseases in the same patient, which implied difficulties at the time of confirming the diagnosis, as well as its care. The analysis of the family tree, a fundamental tool in the determination of genetic diseases, contributed to this diagnosis in the case of both genodermatoses(AU)

Metodología para la atención integral a pacientes con genodermatosis

Las genodermatosis constituyen un grupo de enfermedades genéticas con afectación de la piel y sus anexos. En Cuba, el Programa Nacional de Diagnóstico, Atención y Prevención de Enfermedades Genéticas, en relación a las genodermatosis, no cuenta con protocolos para su diagnóstico, tratamiento y seguimiento. El objetivo del estudio es evaluar una metodología para la atención a los pacientes con genodermatosis. Se realizó en Las Tunas, provincia oriental de Cuba, un estudio cuasi-experimental, aplicándose la variante Delphy del método de expertos, siendo consultados un grupo de especialistas cubanos de dermatología, genética médica clínica y pediatría, con alto nivel científico y experiencia en el trabajo con pacientes con genodermatosis. Diseñándose la metodología que propone el protocolo del diagnóstico, tratamiento y algoritmo de seguimiento para estos pacientes. Se estudiaron 395 pacientes atendidos en el Departamento provincial de Genética Médica. Se estudiaron la tasa de prevalencia, la media de casos diagnosticados por año, la proporción de complicaciones presentadas, el índice de supervivencia e índice de letalidad y para relacionar las variables referentes a la mejoría del estado dermatológico y manifestaciones extracutáneas se utilizó la prueba estadística de Chi cuadrado de Mc-Nemar, con una significación estadística p≤0,05. Después de implementada la metodología, predominó la neurofibromatosis 1, síndrome de Ehlers Danlos clásico e ictiosis vulgar, la media de casos diagnosticados por año aumentó; disminuyeron las complicaciones, predominando las piodermitis (6.13 %); el índice de mortalidad fue bajo (1.27%) con alto índice de supervivencia (98.73%) y mejoría de las manifestaciones dermatológicas (MCNemar X2=90.41558, P=0.000000) y extracutáneas (McNemar X2=24.083334, P=0.000001). La metodología diseñada para la atención a pacientes con genodermatosis fortalece el Programa Nacional de Diagnóstico, Atención y Prevención de Enfermedades Genéticas, demostrando ser efectiva, con mayor número de casos diagnosticados, menor proporción de complicaciones, alta supervivencia, baja letalidad y mejoría clínica de las manifestaciones dermatológicas y extracutáneas.

The genodermatoses constitutes a group of genetic diseases with affectation of the skin and their annexes. In Cuba, the National Program of Diagnostic, Attention and Prevention of Genetic diseases, in relation to the genodermatoses, don't have protocols for their diagnosis, treatment and pursuit. The objective of this study is to evaluate a methodology for the attention to the patients with genodermatosis. Was carried out in The Tunas, oriental county of Cuba, a quasi-experimental study, being applied the varying Delphy of the method of experts, being consulted a group of Cuban specialists of dermatology, genetics clinical doctor and pediatrics, with high scientific level and experience in the work with patient with genodermatoses. Being designed the methodology that proposes the protocol of the diagnosis, treatment and pursuit algorithm for these patients. 395 patients were studied assisted in the provincial Department of Medical Genetics. Were studied the prevalence rate, the stocking of cases diagnosed per year, the proportion of presented complications, the index of survival and lethality index and to relate the relating variables to the improvement of the state dermatologic and extracutaneous manifestations the statistical test of square Chi of Mc-Nemar was used, with a significance statistical p≤0,05. After having implemented the methodology, prevailed the neurofibromatosis, Ehlers Danlos syndrome and ichthyosis vulgaris; the stocking of cases diagnosed per year increased; they diminished the complications, prevailing the piodermitis (6.13%); the index of mortality was low (1.27%) with high index of survival (98.73%) and improvement of the manifestations dermatologic (MCNemar X2=90.41558, P=0.000000) and extracutaneous (McNemar X2=24.083334, P=0.000001). The methodology designed for the attention to patient with genodermatoses strengthens the National Program of Diagnostic, Attention and Prevention of Genetic Illnesses, demonstrating to be effective, with bigger number of diagnosed cases, smaller proportion of complications, high survival, low lethality and clinical improvement of the dermatologic and extracutaneous manifestations.

As genodermatoses são um grupo de doenças genéticas com envolvimento da pele e seus anexos. Em Cuba, o Programa Nacional de Diagnóstico, Cuidado e Prevenção de Doenças Genéticas, em relação às genodermatoses, não possui protocolos para seu diagnóstico, tratamento e acompanhamento. O objetivo do estudo é avaliar uma metodologia para o cuidado de pacientes com genodermatose. Um estudo quase-experimental foi realizado em Las Tunas, província oriental de Cuba, aplicando a variante Delphy do método expert, sendo consultado um grupo de especialistas cubanos em dermatologia, genética médica clínica e pediatria, com alto nível científico e experiência no trabalho com pacientes com genodermatose. Desenho da metodologia que propõe o protocolo de diagnóstico, tratamento e algoritmo de acompanhamento para esses pacientes. Um total de 395 pacientes tratados no Departamento Provincial de Genética Médica foram estudados. Foram estudadas as prevalências, o número médio de casos diagnosticados por ano, a proporção de complicações apresentadas, a sobrevida e o índice de letalidade e para relacionar as variáveis referentes à melhora do estado dermatológico e das manifestações extracutâneas, utilizou-se o teste estatístico Qui-quadrado de Mc-Nemar, com significância estatística p≤0, 05. Após a implementação da metodologia, predominaram a neurofibromatose 1, a síndrome clássica de Ehlers Danlos e a ictiose vulgar, aumentando-se o número médio de casos diagnosticados por ano; complicações diminuídas, predominantemente piodermite (6,13%); a taxa de mortalidade foi baixa (1,27%), com alta sobrevida (98,73%) e melhora dermatológica (MCNemar X2=90,41558, P=0,000000) e extracutânea (McNemar X2=24,083334, P=0,000001). A metodologia desenhada para o cuidado de pacientes com genodermatose fortalece o Programa Nacional de Diagnóstico, Cuidado e Prevenção de Doenças Genéticas, mostrando-se eficaz, com maior número de casos diagnosticados, menor proporção de complicações, alta sobrevida, baixa letalidade e melhora clínica das manifestações dermatológicas e extracutâneas.

Congenital Adrenal Hyperplasia and Ehlers-Danlos Syndrome.

Congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase deficiency is an autosomal recessive disorder. The 21-hydroxylase enzyme P450c21 is encoded by the CYP21A2 gene located on chromosome 6p21.33 within the HLA major histocompatibility complex. This locus also contains the CYP21A1P, a non-functional pseudogene, that is highly homologous to the CYP21A2 gene. Other duplicated genes are C4A and C4B, that encode two isoforms of complement factor C4, the RP1 gene that encodes a serine/threonine protein kinase, and the TNXB gene that, encodes the extracellular matrix glycoprotein tenascin-X (TNX). TNX plays a role in collagen deposition by dermal fibroblasts and is expressed in the dermis of the skin and the connective tissue of the heart and skeletal muscle. During meiosis, misalignment may occur producing large gene deletions or gene conversion events resulting in chimeric genes. Chimeric recombination may occur between TNXB and TNXA. Three TNXA/TNXB chimeras have been described that differ in the junction site (CH1 to CH3) and result in a contiguous CYP21A2 and TNXB gene deletion, causing CAH-X syndrome. TNXB deficiency is associated with Ehlers Danlos syndrome (EDS). EDS comprises a clinically and genetically heterogeneous group of connective tissue disorders. As molecular analysis of the TNXB gene is challenging, the TNX-deficient type EDS is probably underdiagnosed. In this minireview, we will address the different strategies of molecular analysis of the TNXB-gene, as well as copy number variations and genetic status of TNXB in different cohorts. Furthermore, clinical features of EDS and clinical recommendations for long-term follow-up are discussed.

The Presentation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Influenced by the Presence or Absence of Joint Hypermobility.

OBJECTIVE: To examine demographic and clinical characteristics of individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with and without joint hypermobility We hypothesized that patients who were joint hypermobility-positive would have an earlier onset of ME/CFS symptoms as well as increased severity, a greater number of comorbid conditions, and a lower health-related quality of life. STUDY DESIGN: From an observational cohort study of 55 individuals meeting the Fukuda criteria for ME/CFS, we compared groups using a Beighton score cutoff of 4 or higher to indicate joint hypermobility. Chart data were collected to examine the age and type of onset of ME/CFS and the presence of comorbid conditions. The impact on quality of life was assessed through questionnaires that included the Peds QL, Functional Disability Inventory, Peds QL Multidimensional Fatigue Scale, and Anxiety Subscale of the Symptom Checklist 90. RESULTS: There was no significant difference between groups in mean ± SD age at onset of ME/CFS (13.3 ± 3.3 years vs 13.3 ± 2.3 years; P = .92), sex, frequency, and severity of ME/CFS symptoms, orthostatic intolerance symptoms, or comorbid conditions. There was no significant difference between the groups in measures of health-related quality of life using a Beighton score cutoff of 4 or a cutoff of 5 to define joint hypermobility. CONCLUSIONS: Despite being a risk factor for the development of ME/CFS, joint hypermobility as defined in this study was not associated with other clinical characteristics of the illness.

Ehlers-Danlos Syndrome: Molecular and Clinical Characterization of TNXA/TNXB Chimeras in Congenital Adrenal Hyperplasia.

CONTEXT: The syndrome CAH-X is due to a contiguous gene deletion of CYP21A2 and TNXB resulting in TNXA/TNXB chimeras. OBJECTIVE: To analyze TNXB gene status and to clinically evaluate the Ehlers-Danlos syndrome phenotype in a large cohort of Argentine congenital adrenal hyperplasia (CAH) patients to assess the prevalence of this condition in our population. METHODS: TNXB gene analysis was performed in 66 nonrelated CAH patients that were carriers of the CYP21A2 gene deletion. A molecular strategy based on multiplex ligation-dependent probe amplification and Sanger sequencing analysis was developed allowing for the detection of different, previously described TNXA/TNXB chimeras, named CH1, CH2, and CH3. The main outcome measures were TNXB status of CAH patients that were carriers of the CYP21A2 deletion in the homozygous or heterozygous state. RESULTS: TNXA/TNXB CH1 was found in 41%, CH2 in 29%, and CH3 in 1% of nonrelated alleles carrying the CYP21A2 deletion. Thus, overall 71% of alleles were found to carry a contiguous gene deletion. Sixty-seven percent of patients analyzed had a monoallelic form and 6% a biallelic form. All patients with the biallelic form had severe skin hyperextensibility and generalized joint hypermobility. CONCLUSION: Based on the high frequency of TNXB alterations found in CYP21A2 deletion carrier alleles, we recommend evaluating TNXB status in these patients, and assessing connective tissue dysplasia, including cardiologic alterations in positive cases. The number of patients undergoing cardiological evaluation should be expanded to determine the incidence of structural and functional abnormalities in this cohort.

Psychosocial and Motor Characteristics of Patients With Hypermobility.

Objectives: To identify psychosocial and motor aspects related to joint hypermobility (JH) in a sample from almost all Brazilian states by age range and sex; to characterize JH by the Beighton total score ≥4, ≥5, and ≥6 according to sex and age and atypicality in the sitting position and in the hands; identify, in the total sample, manifestations of "growing pain" and its location, fatigue, attention deficit, anxiety, insomnia, drowsiness, apathy, depression, delay in walking, not crawling or crawling differently, school performance, spatial orientation and/or temporally impaired, social isolation, and being stigmatized as "lazy/clumsy/apathetic". Methods: This retrospective, observational, quantitative, and cross-sectional study used data obtained through analyses of descriptive and inferential crossings between 2012 and 2020 of 482 medical records of individuals between 1 and 76 years of age, from most Brazilian states. All patients previously diagnosed with "joint hypermobility syndrome" (JHS) and "Ehlers-Danlos syndrome hypermobility type" (EDS-HT) had their medical records reassessed, following the guidelines established in 2017. The analysis of GJH was performed using the updated method by Beighton method; atypical characteristics were investigated in the hands and the ability to sit in the "W" and the "concave" positions. The characteristics and manifestations of "growing pain" and its location were analyzed in the total sample, fatigue, insomnia, drowsiness, apathy, depression, social isolation, attention deficit, anxiety, stigmatization as "lazy," clumsy/restless, impaired school performance, and spatial and/or temporal orientation. Descriptive and inferential statistical methods were used, such as Mean, Median, Mode, Standard Deviation, Standard Error, Maximum Value, Minimum Value, Komolgorov-Smirnov, Significance, Relative Value, Absolute Value, Mann-Whitney U, and Correlation of Spearman. Results: JH in the total sample predominated in the upper limbs, the majority were women, represented by 352 (73.02%), 15 years old or older with 322 (66.80%), 312 (64.73%) had a Beighton total score ≥6, which decreased as the age increased. Always sitting in the "concave" position was represented by 54.15% and the ability to sit in the "W" position by 39.21%; signs on the hands totaled between 27.59 and 44.19% with a significant correlation between the variables. Among the characteristics, fatigue predominated, followed by an awkward/clumsy/restless individual, attention deficit, anxiety and stigmatized as "lazy," insomnia, drowsiness, apathy, depression, impaired spatial and/or temporal orientation, and social isolation. From the total sample, pain in the lower limbs was reported by 55.81% and having or having had "growing pain" was reported by 36.93%, delay in walking occurred in 19.92%, 15.35% did not crawl or crawled differently, and for 12.86%, school performance was impaired. Higher Beighton total scores showed a trend towards motor implications and correlation between variables. Ability to still sit in the "concave" position was possible for 54.15% and to sit in the "W" position for 39.21%. Conclusion: In the total sample, the JH characteristic prevails in the upper limbs of female children, adolescents and adults, with a total Beighton score ≥6. Most sit in the "concave" position and less than half also sit in the "W" position and with atypical hand postures. The higher Beighton scores, which include the upper limbs, show a tendency to not crawl or crawl differently, delayed ambulation, and impaired school performance. The predominance of JH in the upper limbs is suggestive of a justification for not crawling or crawling differently. Characteristics of atypical motor performance in hands and sitting posture, in addition to fatigue, pain since childhood, anxiety, apathy, depression, sleep disorders, stigmatization, attention deficit, spatial and/or temporal orientation impairment, and social isolation are characteristics. suggestive of psychosocial implications at different ages. Future studies with motor and psychosocial aspects of people with JH will help to identify the phenotype of this population and consequent guidance for clinical management based on the motor and psychosocial aspects of people with JH.

Cutaneous asthenia in a domestic cat (Felis silvestris catus)

Background: Cutaneous asthenia or Ehlers-Danlos syndrome is an inherited and rare disease. This infirmity is from an autosomal mutation that influences the collagen synthesis of the carrier. Thus, its skeleton, formed of fibers, is structurally defective. The disease is characterized by hyperelasticity and skin fragility, leading to lesions throughout the skin. The lesions may manifest in specific places or in a generalized way, being more frequent in the limbs, neck, and back. This disease does not have a specific treatment, only management care to avoid new traumas. Case: A 3-year-old male castrated, no defined race cat, was attended at one veterinary clinic with a history of intense itching. The rapid tests for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) were negative. On physical examination, infestation by fleas, lesions all over the body, and skin hyperelasticity were observed. Topical treatment for ectoparasites as well as for body wounds was established. After the treatment, he returned without itching, but with the complaints of new lesions that did not heal. The patient underwent a total shearing to facilitate the treatment of the skin, and then he underwent blood tests, biochemistry, hormonal tests, and ultrasound, which showed no suggestive changes for hyperadrenocorticism and diabetes mellitus. His clinical signs, besides not matching with these diseases, also did not indicate skin fragility due to his history of age and balanced diet. The confirmation of the cutaneous asthenia syndrome was acquired through biopsy of skin fragment, in which it was observed disarray of collagen fibers, hypertrophy, and fibroblast hyperplasia, together with the rate of extensibility of the skin where the value reached the mark of 27.5%. Throughout the hospitalization, it was noted the progression of the disease with the appearance of new lesions, where there was no bleeding and they appeared even with the patient wearing padded clothes. Its progression lasted one year until the patient's euthanasia. Discussion: For the disposal of diabetes mellitus and hyperadrenocorticism as causes of the appearance of lesions by the body in the patient, he was submitted to the suppression tests with dexamethasone, in which he presented normality, in the biochemical examination it was dosed with fructosamine and glucose. The fructosamine was in the reference value, but the glucose was slightly altered, this increase may have been a result of stress at the time of blood collection. In addition to the patient not showing specific clinical signs such as polyphagia, polyuria, polydipsia, and weight loss, these are characteristic clinical signs of the disease. For the diagnosis of Ehlers-Danlos syndrome, histological examination, and calculation of the skin extensibility index were used, where the results obtained confirmed the suspicion. This genetic anomaly has no treatment, being progressive, so only environmental management is done to mitigate the appearance of the lesions and provide animal welfare. This case report contributes to aggregating the scientific literature in the area of veterinary medicine since skin asthenia is a rare disease and when its extent is total it becomes even more atypical. The availability of this article will provide a vision of palliative treatment for other cases, demonstrating the progressive nature of the lesions and the methods of diagnosis.

Estudios de agregación plaquetaria como endofenotipo de las alteraciones hereditarias de la fibra colágena / Platelet aggregation studies as an endophenotype of hereditary disorders of collagen fiber

Introducción: Las plaquetas contribuyen a la hemostasia y la interrupción heredada o adquirida; en sus procesos bioquímicos pueden alterar la función plaquetaria. Estos trastornos de agregación se han asociado a enfermedades genéticas con afectación del tejido conectivo como el síndrome Ehlers-Danlos, cuyo diagnóstico diferencial con el espectro de hipermovilidad articular resulta difícil clínica y molecularmente. Estas entidades con afectación en las fibras colágenas y diferente repercusión clínica precisan diferenciales en su diagnóstico clínico. Métodos: Se revisaron 353 historias clínicas de pacientes atendidos en el Servicio de Genética del Hospital Pediátrico William Soler desde septiembre del 2009 al 2012, con diagnóstico de hipermovilidad articular por criterios de Beighton y de Ehlers-Danlos según Villefranche (1997). Se incluyó a los pacientes de 5-18 años con resultados documentados del estudio de agregación plaquetaria, valorados por especialistas en hematología. Resultados: Se encontraron trastornos de agregación plaquetaria en 79 de 86 pacientes (92 por ciento). En 7 casos con hipermovilidad de 65 con este diagnóstico (10 por ciento), los resultados fueron negativos. Los 21 con síndrome Ehlers-Danlos tuvieron afectaciones con los fosfolípidos plaquetarios. La hipermovilidad articular estuvo asociada a la combinación difosfato de adenosina (ADP)-epinefrina y el Ehlers-Danlos a la combinación ADP-epinefrina-colágeno-fosfolípidos. Conclusiones: Los pacientes con hipermovilidad articular mostraron asociación a defectos de liberación de gránulos con agonistas como el ADP-epinefrina y los Ehlers-Danlos con la disponibilidad de los fosfolípidos, relacionados con el cambio de forma plaquetaria. Este resultado puede ser una herramienta para conocer el endofenotipo funcional plaquetario como elemento diferencial en los trastornos de la fibra colágena(AU)

Introduction: Platelets contribute to hemostasis and inherited or acquired interruption; in its biochemical processes it can alter platelet function. These aggregation disorders have been associated with genetic diseases with connective tissue involvement such as Ehlers-Danlos syndrome, whose differential diagnosis with the spectrum of joint hypermobility is clinically and molecularly difficult. These entities with involvement of the collagen fibers and different clinical repercussions require differentials in their clinical diagnosis. Methods: 353 medical records of patients attended in the Genetics service of the William Soler Pediatric Hospital from September 2009 to 2012, with a diagnosis of joint hypermobility by Beighton and Ehlers-Danlos criteria according to Villefranche (1997) were reviewed. Patients aged 5-18 years were included with documented results of the platelet aggregation study, assessed by specialists in hematology. Results: Platelet aggregation disorders were found in 79 of 86 patients (92 percent). In 7 cases with hypermobility of 65 with this diagnosis (10 percent), the results were negative. The 21 with Ehlers-Danlos syndrome had affectations with platelet phospholipids. Joint hypermobility was associated with the combination adenosine diphosphate (ADP) -epinephrine and the Ehlers-Danlos with the combination ADP-epinephrine-collagen-phospholipids. Conclusions: Patients with joint hypermobility showed an association to granule release defects with agonists such as ADP-epinephrine and Ehlers-Danlos with the availability of phospholipids, related to platelet shape change. This result can be a tool to know the platelet functional endophenotype as a differential element in collagen fiber disorders(AU)

Autosomal recessive inheritance of cutaneous asthenia in a dog: case report / Astenia cutânea autossômica recessiva em cão: relato de caso

Cutaneous asthenia (CA) or Ehlers-Danlos Syndrome, in dogs, is a rare hereditary syndrome caused by autosomal dominant inheritance that causes collagen synthesis failure and leads to hyperextensibility and cutaneous fragility. This report describes a clinical case of canine CA of hereditary recessive origin, hitherto proven for other species, in an animal born from inbreeding healthy parents. A one-year-old female Maltese dog received clinical and surgical care for a cutaneous wound after a hygienic bath. The clinical history revealed the occurrence of other injuries that were caused by minor trauma and the consanguinity of the patient. During wound cleaning, the trichotomy and removal of an adhesive tape that was fixed to the skin generated new lacerations, which led to clinical suspicion of CA. CA was confirmed by calculating the cutaneous extensibility index (CEI), which was 22%, higher than the normal limit for the species (14.5%). The skin biopsy confirmed the clinical diagnosis, and the wound of the animal was treated routinely and healed clinically. Both dominant and recessive patterns have been well documented in cats; however, in dogs, only the dominant form has been reported in the literature. Our findings demonstrate that canine CA may result from autosomal recessive inheritance, and CA must be considered during diagnostic clinical approaches and breeding selections.(AU)

A astenia cutânea (CA) ou Síndrome de Ehlers-Danlos, em cães, é uma síndrome hereditária rara, causada por gene autossômico dominante que resulta em falha na síntese de colágeno levando à hiperextensibilidade e à fragilidade cutâneas. O objetivo deste trabalho é relatar a existência de astenia cutânea canina de origem hereditária recessiva, até agora comprovada para outras espécies, a partir da descrição de um caso clínico de CA em um animal nascido de união consanguínea de pais saudáveis. Uma cadela Maltês, com um ano de idade, recebeu atendimento clínico-cirúrgico por apresentar uma ferida cutânea após um banho higiênico. A história clínica revelou a ocorrência de outros ferimentos provocados por pequenos traumas e a origem consanguínea da paciente. Durante a limpeza da ferida, a tricotomia e a remoção de uma fita adesiva fixada à pele geraram novas lacerações levantando à suspeita clínica de astenia cutânea, confirmada pelo cálculo do índice de extensibilidade cutânea (CEI) que resultou em 22%, valor superior ao limítrofe de normalidade para a espécie (14,5%). A biopsia cutânea confirmou o diagnóstico clínico. A ferida do animal foi tratada rotineiramente resultando em cura clínica. Tanto as formas dominante e recessiva foram bem documentadas em gatos; entretanto, em cães, somente a forma dominante havia sido descrita pela literatura. Concluiu-se que a astenia cutânea canina pode advir de herança autossômica recessiva e isto deve ser considerado durante a abordagem clínica visando o diagnóstico e a seleção racial.(AU)

Autosomal recessive inheritance of cutaneous asthenia in a dog: case report / Astenia cutânea autossômica recessiva em cão: relato de caso

Cutaneous asthenia (CA) or Ehlers-Danlos Syndrome, in dogs, is a rare hereditary syndrome caused by autosomal dominant inheritance that causes collagen synthesis failure and leads to hyperextensibility and cutaneous fragility. This report describes a clinical case of canine CA of hereditary recessive origin, hitherto proven for other species, in an animal born from inbreeding healthy parents. A one-year-old female Maltese dog received clinical and surgical care for a cutaneous wound after a hygienic bath. The clinical history revealed the occurrence of other injuries that were caused by minor trauma and the consanguinity of the patient. During wound cleaning, the trichotomy and removal of an adhesive tape that was fixed to the skin generated new lacerations, which led to clinical suspicion of CA. CA was confirmed by calculating the cutaneous extensibility index (CEI), which was 22%, higher than the normal limit for the species (14.5%). The skin biopsy confirmed the clinical diagnosis, and the wound of the animal was treated routinely and healed clinically. Both dominant and recessive patterns have been well documented in cats; however, in dogs, only the dominant form has been reported in the literature. Our findings demonstrate that canine CA may result from autosomal recessive inheritance, and CA must be considered during diagnostic clinical approaches and breeding selections.

A astenia cutânea (CA) ou Síndrome de Ehlers-Danlos, em cães, é uma síndrome hereditária rara, causada por gene autossômico dominante que resulta em falha na síntese de colágeno levando à hiperextensibilidade e à fragilidade cutâneas. O objetivo deste trabalho é relatar a existência de astenia cutânea canina de origem hereditária recessiva, até agora comprovada para outras espécies, a partir da descrição de um caso clínico de CA em um animal nascido de união consanguínea de pais saudáveis. Uma cadela Maltês, com um ano de idade, recebeu atendimento clínico-cirúrgico por apresentar uma ferida cutânea após um banho higiênico. A história clínica revelou a ocorrência de outros ferimentos provocados por pequenos traumas e a origem consanguínea da paciente. Durante a limpeza da ferida, a tricotomia e a remoção de uma fita adesiva fixada à pele geraram novas lacerações levantando à suspeita clínica de astenia cutânea, confirmada pelo cálculo do índice de extensibilidade cutânea (CEI) que resultou em 22%, valor superior ao limítrofe de normalidade para a espécie (14,5%). A biopsia cutânea confirmou o diagnóstico clínico. A ferida do animal foi tratada rotineiramente resultando em cura clínica. Tanto as formas dominante e recessiva foram bem documentadas em gatos; entretanto, em cães, somente a forma dominante havia sido descrita pela literatura. Concluiu-se que a astenia cutânea canina pode advir de herança autossômica recessiva e isto deve ser considerado durante a abordagem clínica visando o diagnóstico e a seleção racial.

Autosomal recessive inheritance of cutaneous asthenia in a dog - case report / Astenia cutânea autossômica recessiva em cão - relato de caso

Cutaneous asthenia (CA) or Ehlers-Danlos Syndrome, in dogs, is a rare hereditary syndrome caused by autosomal dominant inheritance that causes collagen synthesis failure and leads to hyperextensibility and cutaneous fragility. This report describes a clinical case of canine CA of hereditary recessive origin, hitherto proven for other species, in an animal born from inbreeding healthy parents. A one-year-old female Maltese dog received clinical and surgical care for a cutaneous wound after a hygienic bath. The clinical history revealed the occurrence of other injuries that were caused by minor trauma and the consanguinity of the patient. During wound cleaning, the trichotomy and removal of an adhesive tape that was fixed to the skin generated new lacerations, which led to clinical suspicion of CA. CA was confirmed by calculating the cutaneous extensibility index (CEI), which was 22%, higher than the normal limit for the species (14.5%). The skin biopsy confirmed the clinical diagnosis, and the wound of the animal was treated routinely and healed clinically. Both dominant and recessive patterns have been well documented in cats; however, in dogs, only the dominant form has been reported in the literature. Our findings demonstrate that canine CA may result from autosomal recessive inheritance, and CA must be considered during diagnostic clinical approaches and breeding selections.

A astenia cutânea (CA) ou Síndrome de Ehlers-Danlos, em cães, é uma síndrome hereditária rara, causada por gene autossômico dominante que resulta em falha na síntese de colágeno levando à hiperextensibilidade e à fragilidade cutâneas. O objetivo deste trabalho é relatar a existência de astenia cutânea canina de origem hereditária recessiva, até agora comprovada para outras espécies, a partir da descrição de um caso clínico de CA em um animal nascido de união consanguínea de pais saudáveis. Uma cadela Maltês, com um ano de idade, recebeu atendimento clínico-cirúrgico por apresentar uma ferida cutânea após um banho higiênico. A história clínica revelou a ocorrência de outros ferimentos provocados por pequenos traumas e a origem consanguínea da paciente. Durante a limpeza da ferida, a tricotomia e a remoção de uma fita adesiva fixada à pele geraram novas lacerações levantando à suspeita clínica de astenia cutânea, confirmada pelo cálculo do índice de extensibilidade cutânea (CEI) que resultou em 22%, valor superior ao limítrofe de normalidade para a espécie (14,5%). A biopsia cutânea confirmou o diagnóstico clínico. A ferida do animal foi tratada rotineiramente resultando em cura clínica. Tanto as formas dominante e recessiva foram bem documentadas em gatos; entretanto, em cães, somente a forma dominante havia sido descrita pela

Autosomal recessive inheritance of cutaneous asthenia in a dog - case report / Astenia cutânea autossômica recessiva em cão - relato de caso

Cutaneous asthenia (CA) or Ehlers-Danlos Syndrome, in dogs, is a rare hereditary syndrome caused by autosomal dominant inheritance that causes collagen synthesis failure and leads to hyperextensibility and cutaneous fragility. This report describes a clinical case of canine CA of hereditary recessive origin, hitherto proven for other species, in an animal born from inbreeding healthy parents. A one-year-old female Maltese dog received clinical and surgical care for a cutaneous wound after a hygienic bath. The clinical history revealed the occurrence of other injuries that were caused by minor trauma and the consanguinity of the patient. During wound cleaning, the trichotomy and removal of an adhesive tape that was fixed to the skin generated new lacerations, which led to clinical suspicion of CA. CA was confirmed by calculating the cutaneous extensibility index (CEI), which was 22%, higher than the normal limit for the species (14.5%). The skin biopsy confirmed the clinical diagnosis, and the wound of the animal was treated routinely and healed clinically. Both dominant and recessive patterns have been well documented in cats; however, in dogs, only the dominant form has been reported in the literature. Our findings demonstrate that canine CA may result from autosomal recessive inheritance, and CA must be considered during diagnostic clinical approaches and breeding selections.

A astenia cutânea (CA) ou Síndrome de Ehlers-Danlos, em cães, é uma síndrome hereditária rara, causada por gene autossômico dominante que resulta em falha na síntese de colágeno levando à hiperextensibilidade e à fragilidade cutâneas. O objetivo deste trabalho é relatar a existência de astenia cutânea canina de origem hereditária recessiva, até agora comprovada para outras espécies, a partir da descrição de um caso clínico de CA em um animal nascido de união consanguínea de pais saudáveis. Uma cadela Maltês, com um ano de idade, recebeu atendimento clínico-cirúrgico por apresentar uma ferida cutânea após um banho higiênico. A história clínica revelou a ocorrência de outros ferimentos provocados por pequenos traumas e a origem consanguínea da paciente. Durante a limpeza da ferida, a tricotomia e a remoção de uma fita adesiva fixada à pele geraram novas lacerações levantando à suspeita clínica de astenia cutânea, confirmada pelo cálculo do índice de extensibilidade cutânea (CEI) que resultou em 22%, valor superior ao limítrofe de normalidade para a espécie (14,5%). A biopsia cutânea confirmou o diagnóstico clínico. A ferida do animal foi tratada rotineiramente resultando em cura clínica. Tanto as formas dominante e recessiva foram bem documentadas em gatos; entretanto, em cães, somente a forma dominante havia sido descrita pela

Hipermovilidad articular y Síndrome de Ehlers-Danlos: consideraciones desde el cuidado en enfermería

Los desórdenes del espectro hipermóvil y síndrome de Ehlers-Danlos (HSD y EDS por sus siglas en inglés) son enfermedades crónicas, consideradas extrañas y que afectan la calidad de vida de estos pacientes. Según estudios internacionales, su prevalencia mundial se encuentra entre el 2 al 57 % de la población, presentando, según la etapa de vida, manifestaciones clínicas variadas. Además, pueden ocurrir exacerbaciones de otras condiciones asociadas, por lo que se torna difícil diagnosticar y se generan múltiples consultas en los distintos niveles de atención. En consecuencia, este escrito reflexiona respecto a la importancia del rol profesional de enfermería en la gestión del cuidado de niños y adultos que viven con este problema de salud, mediante una revisión de publicaciones actualizadas en torno a HSD y EDS. Se enfatiza sobre cómo desde el cuidado de enfermería se puede acompañar a las personas con esta condición. Se concluye que es primordial tomar conciencia de la existencia de esta enfermedad de forma interdisciplinaria, para aportar en la pesquisa, el manejo y cuidado de las personas afectadas.

SUMMARY Hypermobile spectrum disorders and Ehlers-Danlos syndrome (HSD and EDS) are chronic diseases, considered unusual and affecting the quality of life of these patients. According to international studies, its prevalence worldwide is between 2 to 57% of the population and presenting, depending on the stage of life, varied clinical manifestations. Also, exacerbations of other associated conditions may occur, which makes it difficult to diagnose, generating several consults at the different levels of care. Consequently, this paper reflects on the importance of the nurse professional role in managing the care of children and adults living with this health problem, through a review of updated publications on HSD and EDS. Emphasis is placed on how nursing care can accompany people with this condition. It is concluded that it is essential to be aware of the existence of this pathology in an interdisciplinary way to contribute in the research, the management and care of the affected people.