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Journal: American journal of medical genetics. Part C, Seminars in medical genetics

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Chronic pain in the Ehlers-Danlos syndromes (EDS) is common and may be severe. According to one study, nearly 90% of patients report some form of chronic pain. Pain, which is often one of the first symptoms to occur, may be widespread or localized to one region such as an arm or a leg. Studies on treatment modalities are few and insufficient to guide management. The following is a discussion of the evidence regarding the underlying mechanisms of pain in EDS. The causes of pain in this condition are multifactorial and include joint subluxations and dislocations, previous surgery, muscle weakness, proprioceptive disorders, and vertebral instability. Affected persons may also present with generalized body pain, fatigue, headaches, gastrointestinal pain, temporomandibular joint pain, dysmenorrhea, and vulvodynia. Pain management strategies may be focused around treating the cause of the pain (e.g., dislocation of a joint, proprioceptive disorder) and minimizing the sensation of pain. Management strategies for chronic pain in EDS includes physical therapy, medications, as well as durable medical equipment such as cushions, compressive garments, and braces. The different modalities are discussed in this paper. © 2017 Wiley Periodicals, Inc.

Concepts: Medicine, Symptoms, Joint, Pain, Ehlers-Danlos syndrome, Temporomandibular joint, Temporomandibular joint disorder, Joint dislocation

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Autonomic dysfunction contributes to health-related impairment of quality of life in the hypermobile type of Ehlers-Danlos syndrome (hEDS). Typical signs and symptoms include tachycardia, hypotension, gastrointestinal dysmotility, and disturbed bladder function and sweating regulation. Cardiovascular autonomic dysfunction may present as Orthostatic Intolerance, Orthostatic Hypotension, Postural Orthostatic Tachycardia Syndrome, or Neurally Mediated Hypotension. The incidence, prevalence, and natural history of these conditions remain unquantified, but observations from specialist clinics suggest they are frequently seen in hEDS. There is growing understanding of how hEDS-related physical and physiological pathology contributes to the development of these conditions. Evaluation of cardiovascular symptoms in hEDS should include a careful history and clinical examination. Tests of cardiovascular function range from clinic room observation to tilt-table assessment to other laboratory investigations such as supine and standing catecholamine levels. Non-pharmacologic treatments include education, managing the environment to reduce exposure to triggers, improving cardiovascular fitness, and maintaining hydration. Although there are limited clinical trials, the response to drug treatments in hEDS is supported by evidence from case and cohort observational data, and short-term physiological studies. Pharmacologic therapy is indicated for patients with moderate-severe impairment of daily function and who have inadequate response or tolerance to conservative treatment. Treatment in hEDS often requires a focus on functional maintenance. Also, the negative impact of cardiovascular symptoms on physical and psycho-social well-being may generate a need for a more general evaluation and on-going management and support. © 2017 Wiley Periodicals, Inc.

Concepts: Cardiology, The Canon of Medicine, Marfan syndrome, Orthostatic hypotension, Postural orthostatic tachycardia syndrome, Ehlers-Danlos syndrome, Dysautonomia, Orthostatic intolerance

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The hypermobile type of Ehlers-Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue. It has been described largely in those with musculoskeletal complaints including joint hypermobility, joint subluxations/dislocations, as well as skin and soft tissue manifestations. Many patients report activity-related pain and some go on to have daily pain. Two undifferentiated syndromes have been used to describe these manifestations-joint hypermobility syndrome and hEDS. Both are clinical diagnoses in the absence of other causation. Current medical literature further complicates differentiation and describes multiple associated symptoms and disorders. The current EDS nosology combines these two entities into the hypermobile type of EDS. Herein, we review and summarize the literature as a better clinical description of this type of connective tissue disorder. © 2017 Wiley Periodicals, Inc.

Concepts: Collagen, The Canon of Medicine, Syndromes, Marfan syndrome, Connective tissue, Ehlers-Danlos syndrome, Hypermobility, Contortion

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The genetic counseling profession is continuing to develop globally, with countries in various stages of development. In some, the profession has been in existence for decades and is increasingly recognized as an important provider of allied health, while in others it is just beginning. In this article, we describe the current global landscape of the genetic counseling specialty field’s professional development. Using examples of the United States, United Kingdom, Canada, Australia, South Africa, and various countries in Asia, we highlight the following: (a) status of genetic counseling training programs, (b) availability of credentialing through government and professional bodies (certification, registration, and licensure), and potential for international reciprocity, © scope of clinical practice, and (d) health-care system disparities and cultural differences impacting on practice. The successful global implementation of precision medicine will require both an increased awareness of the importance of the profession of “genetic counselor” and flexibility in how genetic counselors are incorporated into each country’s health-care market. In turn, this will require more collaboration within and across nations, along with continuing engagement of existing genetic counseling professional societies.

Concepts: Medicine, United States, Profession, Canada, Counseling, Medical genetics, Genetic counseling, Licensure

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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.

Concepts: Collagen, Mandible, Joint, Connective tissue, Ehlers-Danlos syndrome, Temporomandibular joint, Temporomandibular joint disorder, Masseteric nerve

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Sex chromosome constitution varies in the human population, both between the sexes (46,XX females and 46,XY males), and within the sexes (e.g., 45,X and 46,XX females, and 47,XXY and 46,XY males). Coincident with this genetic variation are numerous phenotypic differences between males and females, and individuals with sex chromosome aneuploidy. However, the molecular mechanisms by which sex chromosome constitution impacts phenotypes at the cellular, tissue, and organismal levels remain largely unexplored. Thus, emerges a fundamental question connecting the study of sex differences and sex chromosome aneuploidy syndromes: How does sex chromosome constitution influence phenotype? Here, we focus on Turner syndrome (TS), associated with the 45,X karyotype, and its synergies with the study of sex differences. We review findings from evolutionary studies of the sex chromosomes, which identified genes that are most likely to contribute to phenotypes as a result of variation in sex chromosome constitution. We then explore strategies for investigating the direct effects of the sex chromosomes, and the evidence for specific sex chromosome genes impacting phenotypes. In sum, we argue that integrating the study of TS with sex differences offers a mutually beneficial alliance to identify contributions of the sex chromosomes to human development, health, and disease.

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Holoprosencephaly is a spectrum of congenital defects of forebrain development characterized by incomplete separation of the cerebral hemispheres. In vivo diagnosis can be established with prenatal brain imaging and disease severity correlates with extent of abnormally developed brain tissue. Advances in magnetic resonance imaging (MRI) over the past 25 years and their application to the fetus have enabled diagnosis of holoprosencephaly in utero. Here, we report on the prenatal diagnosis of holoprosencephaly using MRI as part of a diagnostic and management evaluation at a tertiary and quaternary referral center. Using an advanced MRI protocol and a 1.5-Tesla magnet, we show radiographic data diagnostic for the holoprosencephaly spectrum, including alobar, semilobar, lobar, middle interhemispheric, and septopreoptic variant. Accurate prenatal evaluation is important because the severity of imaging findings correlates with postnatal morbidity and mortality in holoprosencephaly. Therefore, this work has implications for the evaluation, diagnosis, management, and genetic counseling that families can receive during a pregnancy.

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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.

Concepts: Bone, Medicine, Syndromes, Orthopedic surgery, Reconstructive surgery

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There is increasing amount of evidence pointing toward a high prevalence of psychiatric conditions among individuals with hypermobile type of Ehlers-Danlos syndrome (JHS/hEDS). A literature review confirms a strong association between anxiety disorders and JHSh/hEDS, and there is also limited but growing evidence that JHSh/hEDS is also associated with depression, eating, and neuro-developmental disorders as well as alcohol and tobacco misuse. The underlying mechanisms behind this association include genetic risks, autonomic nervous system dysfunction, increased exteroceptive and interoceptive mechanisms and decreased proprioception. Recent neuroimaging studies have also shown an increase response in emotion processing brain areas which could explain the high affective reactivity seen in JHS/hEDS. Management of these patients should include psychiatric and psychological approaches, not only to relieve the clinical conditions but also to improve abilities to cope through proper drug treatment, psychotherapy, and psychological rehabilitation adequately coupled with modern physiotherapy. A multidimensional approach to this “neuroconnective phenotype” should be implemented to ensure proper assessment and to guide for more specific treatments. Future lines of research should further explore the full dimension of the psychopathology associated with JHS/hEDS to define the nature of the relationship. © 2017 Wiley Periodicals, Inc.

Concepts: Psychology, Brain, Neuroscience, Syndromes, Clinical psychology, Psychiatry, Emotion, Ehlers-Danlos syndrome

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There is increasing recognition that genomic medicine as part of individualized medicine has a defined role in patient care. Rapid advances in technology and decreasing cost combine to bring genomic medicine closer to the clinical practice. There is also growing evidence that genomic-based medicine can advance patient outcomes, tailor therapy and decrease side effects. However the challenges to integrate genomics into the workflow involved in patient care remain vast, stalling assimilation of genomic medicine into mainstream medical practice. In this review we describe the approach taken by one institution to further individualize medicine by offering, executing and interpreting whole exome sequencing on a clinical basis through an enterprise-wide, standalone individualized medicine clinic. We present our experience designing and executing such an individualized medicine clinic, sharing lessons learned and describing early implementation outcomes. © 2014 Wiley Periodicals, Inc.

Concepts: Health care, Medicine, Clinical trial, Patient, Hospital, Physician, Illness, Doctor-patient relationship