Latest EDS Research: March 2015

The March 2015 issue of American Journal of Medical Genetics, a peer-reviewed medical journal dealing with human genetics, is devoted to EDS/JHS. Unfortunately, I don’t have access to the full articles, but I’ve annotated these 9 abstracts from PubMed:

  • Generalized joint hypermobility, joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type.
  • Psychopathological manifestations of joint hypermobility and joint hypermobility syndrome/ Ehlers-Danlos syndrome, hypermobility type: The link between connective tissue and psychological distress revised.
  • The neuromuscular differential diagnosis of joint hypermobility.
  • Phenotypic variability in developmental coordination disorder: Clustering of generalized joint hypermobility with attention deficit/hyperactivity disorder, atypical swallowing and narrative difficulties.
  • Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives. – PubMed – NCBI
  • Connective tissue, Ehlers-Danlos syndrome(s), and head and cervical pain
  • Gastrointestinal and nutritional issues in joint hypermobility syndrome/ehlers-danlos syndrome, hypermobility type.
  • The role of narrative medicine in the management of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.
  • Re-writing the natural history of pain and related symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type | 2013 Dec;

Generalized joint hypermobility, joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type. – PubMed – NCBI – Mar 2015

This issue of the American Journal of Medical Genetics Seminar Series Part C is dedicated to generalized joint hypermobility (gJHM), joint hypermobility syndrome (JHS), and Ehlers-Danlos syndrome, hypermobility type (EDS-HT).

gJHM is the best known clinical manifestation of inherited defects of the connective tissue. On the other side, JHS and EDS-HT are actually considered one and the same from a clinical perspective by most practitioners and researchers (i.e., JHS/EDS-HT), and their molecular basis remains unknown.

For decades, “non-syndromic” gJHM and JHS/EDS-HT have been thought to be simple clinical curiosities or an asset for the “affected” individual. In recent years, the attention on these partially overlapping phenotypes has increased, as they are now recognized risk factors for a series of non-communicable diseases and long-term disabilities. 

This series consists of papers focused on three main topics, namely

(i) assessment and differential diagnosis of children and adults with gJHM,

(ii) systematic presentation of selected key non-articular manifestations of JHS/EDS-HT and actual perception of physiotherapy as the best therapeutic resource for this condition, and

(iii) exploration of the available knowledge relating “congenital laxity of tissues” to various dysfunctions of the nervous system during development and adulthood.

The contributors hope that this collection raises attention to this fascinating field of knowledge, which seems to have ramifications in virtually all medical disciplines

Psychopathological manifestations of joint hypermobility and joint hypermobility syndrome/ Ehlers-Danlos syndrome, hypermobility type:… – PubMed – NCBI: The link between connective tissue and psychological distress revised. – Mar 2015

Psychological distress is a known feature of generalized joint hypermobility (gJHM), as well as of its most common syndromic presentation, namely Ehlers-Danlos syndrome, hypermobility type (a.k.a. joint hypermobility syndrome – JHS/EDS-HT), and significantly contributes to the quality of life of affected individuals.

Most published articles dealt with the link between gJHM (or JHS/EDS-HT) and anxiety-related conditions, and a novel generation of studies is emerging aimed at investigating the psychopathologic background of such an association. In this paper, literature review was carried out with a semi-systematic approach spanning the entire spectrum of psychopathological findings in gJHM and JHS/EDS-HT.

Interestingly, in addition to the confirmation of a tight link between anxiety and gJHM, preliminary connections with

  • depression,
  • attention deficit (and hyperactivity) disorder,
  • autism spectrum disorders, and
  • obsessive-compulsive personality disorder

were also found.

Few papers investigated the relationship with schizophrenia with contrasting results. The mind-body connections hypothesized on the basis of available data were discussed with focus on somatotype, presumed psychopathology, and involvement of the extracellular matrix in the central nervous system.

The hypothesis of positive Beighton score and alteration of interoceptive/proprioceptive/body awareness as possible endophenotypes in families with symptomatic gJHM or JHS/EDS-HT is also suggested. Concluding remarks addressed the implications of the psychopathological features of gJHM and JHS/EDS-HT in clinical practice.

The neuromuscular differential diagnosis of joint hypermobility. – PubMed – NCBI – Mar 2015

Joint hypermobility is the defining feature of various inherited connective tissue disorders such as Marfan syndrome and various types of Ehlers-Danlos syndrome and these will generally be the first conditions to be considered by geneticists and pediatricians in the differential diagnosis of a patient presenting with such findings.

However, several congenital and adult-onset inherited myopathies also present with joint hypermobility in the context of often only mild-to-moderate muscle weakness and should, therefore, be included in the differential diagnosis of joint hypermobility.

In fact, on the molecular level disorders within both groups represent different ends of the same spectrum of inherited extracellular matrix (ECM) disorders.

In this review we will summarize the measures of joint hypermobility, illustrate molecular mechanisms these groups of disorders have in common, and subsequently discuss the clinical features of:

1) the most common connective tissue disorders with myopathic or other neuromuscular features: Ehlers-Danlos syndrome, Marfan syndrome and Loeys-Dietz syndrome;

2) myopathy and connective tissue overlap disorders (muscle extracellular matrix (ECM) disorders), including collagen VI related dystrophies and FKBP14 related kyphoscoliotic type of Ehlers-Danlos syndrome; and

3) various (congenital) myopathies with prominent joint hypermobility including RYR1- and SEPN1-related myopathy. The aim of this review is to assist clinical geneticists and other clinicians with recognition of these disorders.

 Phenotypic variability in developmental coordination disorder: Clustering of generalized joint hypermobility with attention deficit/hyperactivity disorder, atypical swallowing and narrative difficulties – PubMed – NCBI – Mar 2015

Developmental coordination disorder (DCD) is a recognized childhood disorder mostly characterized by motor coordination difficulties. Joint hypermobility syndrome, alternatively termed Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly featuring generalized joint hypermobility (gJHM), musculoskeletal pain, and minor skin features.

Although these two conditions seem apparently unrelated, recent evidence highlights a high rate of motor and coordination findings in children with gJHM or JHS/EDS-HT.

Here, we investigated the prevalence of gJHM in 41 Italian children with DCD in order to check for the existence of recognizable phenotypic subgroups of DCD in relation to the presence/absence of gJHM.

All patients were screened for Beighton score and a set of neuropsychological tests for motor competences (Movement Assessment Battery for Children and Visual-Motor Integration tests), and language and learning difficulties (Linguistic Comprehension Test, Peabody Picture Vocabulary Test, Boston Naming Test, Bus Story Test, and Memoria-Training tests).

All patients were also screening for selected JHS/EDS-HT-associated features and swallowing problems.

  • Nineteen (46%) children showed gJHM and 22 (54%) did not.
  • Children with DCD and gJHM showed a significant excess of frequent falls (95 vs. 18%),
  • easy bruising (74 vs. 0%), motor impersistence (89 vs. 23%), sore hands for writing (53 vs. 9%),
  • attention deficit/hyperactivity disorder (89 vs. 36%),
  • constipation (53 vs. 0%), arthralgias/myalgias (58 vs. 4%),
  • narrative difficulties (74 vs. 32%),
  • and atypical swallowing (74 vs. 18%).

This study confirms the non-causal association between DCD and gJHM, which, in turn, seems to increase the risk for non-random additional features. The excess of language, learning, and swallowing difficulties in patients with DCD and gJHM suggests a wider effect of lax tissues in the development of the nervous system.

Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives. – PubMed – NCBI – Mar 2015

In the last decade, increasing attention has been devoted to the extra-articular and extra-cutaneous manifestations of joint hypermobility syndrome, also termed Ehlers-Danlos syndrome, hypermobility type (i.e., JHS/EDS-HT).

Despite the fact that the current diagnostic criteria for both disorders remain focused on joint hypermobility, musculoskeletal pain and skin changes, medical practice and research have started investigating a wide spectrum of visceral, neurological and developmental complications, which represent major burdens for affected individuals.

In particular, children with generalized joint hypermobility often present with various neurodevelopmental issues and can be referred for neurological consultation.

It is common that investigations in these patients yield negative or inconsistent results, eventually leading to the exclusion of any structural neurological or muscle disorder. In the context of specialized clinics for connective tissue disorders, a clear relationship between generalized joint hypermobility and a characteristic neurodevelopmental profile affecting coordination is emerging.

The clinical features of these patients tend to overlap with those of developmental coordination disorder and can be associated with learning and other disabilities.

Physical and psychological consequences of these additional difficulties add to the chief manifestations of the pre-existing connective tissue disorder, affecting the well-being and development of children and their families.

In this review, particular attention is devoted to the nature of the link between joint hypermobility, coordination difficulties and neurodevelopmental issues in children. Presumed pathogenesis and management issues are explored in order to attract more attention on this association and nurture future clinical research

Connective tissue, Ehlers-Danlos syndrome(s), and head and cervical pain. – PubMed – NCBI – Mar 2015

Ehlers-Danlos syndrome (EDS) is an umbrella term for a growing group of hereditary disorders of the connective tissue mainly manifesting with generalized joint hypermobility, skin hyperextensibility, and vascular and internal organ fragility.

In contrast with other well known heritable connective tissue disorders with severe cardiovascular involvement (e.g., Marfan syndrome), most EDS patients share a nearly normal life span, but are severely limited by disabling features, such as pain, fatigue and headache.

In this work, pertinent literature is reviewed with focus on prevalence, features and possible pathogenic mechanisms of headache in EDSs.

Gathered data are fragmented and generally have a low level of evidence.

  • Headache is reported in no less than 1/3 of the patients.
  • Migraine results the most common type in the hypermobility type of EDS.
  • Other possibly related headache disorders include
  • tension-type headache,
  • new daily persistent headache,
  • headache attributed to spontaneous cerebrospinal fluid leakage,
  • headache secondary to Chiari malformation,
  • cervicogenic headache and
  • neck-tongue syndrome, whose association still lacks of reliable prevalence studies.

The underlying pathogenesis seems complex and variably associated with

  • cardiovascular dysautonomia,
  • cervical spine and temporomandibular joint instability/dysfunction,
  • meningeal fragility,
  • poor sleep quality,
  • pain-killer drugs overuse and
  • central sensitization.

Particular attention is posed on a presumed subclinical cervical spine dysfunction.

Standard treatment is always symptomatic and usually unsuccessful. Assessment and management procedures are discussed in order to put some basis for ameliorating the actual patients’ needs and nurturing future research

Gastrointestinal and nutritional issues in joint hypermobility syndrome/ehlers-danlos syndrome, hypermobility type. – PubMed – NCBI – Mar 2015

Gastrointestinal involvement is a well known complication of Ehlers-Danlos syndromes (EDSs), mainly in form of abdominal emergencies due to intestinal/abdominal vessels rupture in vascular EDS.

In the last decade, a growing number of works investigated the relationship between a wide spectrum of chronic gastrointestinal complaints and various EDS forms, among which the hypermobility type (a.k.a. joint hypermobility syndrome; JHS/EDS-HT) was the most studied.

The emerging findings depict a major role for gastrointestinal involvement in the health status and, consequently, management of JHS/EDS-HT patients.

Nevertheless, fragmentation of knowledge limits its impact on practice within the boundaries of highly specialized clinics.

In this paper, literature review on gastrointestinal manifestations in JHS/EDS-HT was carried out and identified papers categorized as

(i) case-control/cohort studies associating (apparently non-syndromic) joint hypermobility and gastrointestinal involvement,

(ii) case-control/cohort studies associating JHS/EDS-HT and gastrointestinal involvement,

(iii) case reports/series on various gastrointestinal complications in (presumed) JHS/EDS-HT, and

(iv) studies reporting gastrointestinal features in heterogeneous EDS patients’ cohorts.

Gastrointestinal manifestations of JHS/EDS-HT were organized and discussed in two categories, 

  1. structural anomalies (i.e., abdominal/diaphragmatic hernias, internal organ/pelvic prolapses, intestinal intussusceptions) and
  2. functional features (i.e., dysphagia, gastro-esophageal reflux, dyspepsia, recurrent abdominal pain, constipation/diarrhea), with emphasis on practice and future implications.

In the second part of this paper, a summary of possible nutritional interventions in JHS/EDS-HT was presented. Supplementation strategies were borrowed from data available for general population with minor modifications in the light of recent discoveries in the pathogenesis of selected JHS/EDS-HT features

The role of narrative medicine in the management of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. – PubMed – NCBI

Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is a hereditary connective tissue disorder affecting every bodily system.

It is largely underdiagnosed by many practitioners, with the result of a considerable delay in diagnosis and, consequently, in the onset of adequate management schedule and treatment.

Patients may also experience to be misbelieved, erroneously considered affected by a psychiatric or psychosomatic disorders, and rejected by the medical profession, which can lead to feelings of anger and resentment.

Patient journeys are often long and complicated, but if doctors allowed the patient time to tell the full story, and were more prepared to think holistically, there may be a far more positive outcome.

Here, the patients’ perspective is presented with a narrative medicine approach, illustrating the tri-dimensional experience of a JHS/EDS-HT patient, who is also a Bowen Practitioner and a medical writer/educator.

Narrative medicine would be invaluable in working with JHS/EDS-HT so that the patient can tell the story, and offer the practitioner a whole picture of her/his suffering and, often, the key for understanding the cause(s).

Once this has been achieved, it might be possible to build upon a more positive and therapeutic dialogue which would result in better treatment and more effective management.

It is also important for doctors to communicate with JHS/EDS-HT experts who will ultimately improve the patient journey and treatment outcomes of such a complex connective tissue disorder.

From earlier issue:

Re-writing the natural history of pain and related symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. – PubMed – NCBI |Am J Med Genet A. 2013 Dec;

Re-writing the natural history of pain and related symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping connective tissue disorders characterized by chronic/recurrent pain, joint instability complications, and minor skin changes.

Fatigue and headache are also common, although are not yet considered diagnostic criteria.

JHS/EDS-HT is a unexpectedly common condition that remains underdiagnosed by most clinicians and pain specialists. This results in interventions limited to symptomatic and non-satisfactory treatments, lacking reasonable pathophysiologic rationale.

In this manuscript the fragmented knowledge on pain, fatigue, and headache in JHS/EDS is presented with review of the available published information and a description of the clinical course by symptoms, on the basis of authors’ experience.

Pathogenic mechanisms are suggested through comparisons with other functional somatic syndromes (e.g., chronic fatigue syndrome, fibromyalgia, and functional gastrointestinal disorders).

The re-writing of the natural history of JHS/EDS-HT is aimed to raise awareness among clinical geneticists and specialists treating chronic pain conditions about pain and other complications of JHS/EDS-HT.

Symptoms’ clustering by disease stage is proposed to investigate both the molecular causes and the symptoms management of JHS/EDS-HT in future studies

 

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