Elsevier

General Hospital Psychiatry

Volume 37, Issue 1, January–February 2015, Pages 24-30
General Hospital Psychiatry

Psychiatric Medical Comorbidity
Joint hypermobility and the heritable disorders of connective tissue: clinical and empirical evidence of links with psychiatry

https://doi.org/10.1016/j.genhosppsych.2014.10.002Get rights and content

Abstract

Objective

The heritable disorders of connective tissue (HDCTs) are a group of genetic disorders affecting connective tissue matrix proteins. Fragility, laxity of tissues and joint hypermobility (JH) are commons features of HDCT for which the prognosis may range from benign to life threatening. JH and HDCTs, especially joint hypermobility syndrome, Ehlers–Danlos syndromes and Marfan syndrome, have been associated with psychiatric symptomatology. We explored the existing knowledge concerning this association in order to provide an overview of mental disorders linked to JH/HDCT, as well as the hypotheses proposed to explain such association.

Method

A comprehensive search of scientific online databases and references lists was conducted, encompassing publications based on quantitative and qualitative research, including case reports.

Results

Psychiatric conditions in which there is some evidence of an association with JH/HDCT are anxiety disorders, depression, schizophrenia, neurodevelopmental disorders (autism, attention deficit/hyperactivity disorder, and developmental coordination disorder), eating disorders, personality disorders and substance use/misuse.

Conclusion

Despite the need of more research, the available data highlight the importance of examining psychiatric symptoms in those affected by JH/HDCT and the importance of providing interventions with a multidisciplinary approach. The relationship between JH/HDCT and mental disorders merits further attention in order to improve current knowledge and clarify a possible common etiology.

Introduction

The heritable disorders of connective tissue (HDCTs) are a group of genetic disorders affecting connective tissue matrix proteins such as collagens, elastins, fibrillins and tenascins. Grahame [1] describes the pathophysiology pertaining to all HDCT: "genetic aberrations affecting these fibrous proteins distort their biochemical structure then in turn to impairment of tensile strength, resulting in enhanced mobility but at a cost of increased fragility, ultimately risking mechanical tissue failure" (p.15). Joint hypermobility (JH), which is an increased distensibility of joints, constitutes a unifying feature of the HDCTs [2], and their exploration may provide the first insight as to the presence of one of the HDCTs [3]. In this regard, the Beighton score [4] is the most widely used method to detect JH (Fig. 1).

The milder and more frequent variation of HDCT is the joint hypermobility syndrome (JHS), which is characterized by JH accompanied by articular and nonarticular manifestations, mainly chronic pain, autonomic dysfunction and gastrointestinal dysmotility [5]. The Brighton criteria [6] (Table 1) included the principal symptoms for the diagnosis of JHS in the absence of biological tests that may detect it. High prevalences (up to 45%) have been reported using these criteria [5]. Despite its frequency, JHS is often underdiagnosed.

Ehlers–Danlos syndrome (EDS) is another HDCT characterized by the presence of JH, skin hyperextensibility, atrophic scarring and generalized tissue fragility. Their prevalence is estimated at 1/5000 [7]. There are several subtypes of EDS, which range from mild to life threatening. Most of subtypes can be diagnosed by means of biochemical and molecular tests [7]. Subtypes are described in the Villefranche classification [8] (Table 2). The classic form of EDS (or types I and II) present with a more spectacular degree of JH with more pronounced subluxation, deformities and skin stretchiness [1]. The EDS hypermobility type (or type III) overlaps with JHS, and some authors consider them to be the same condition [9]. The EDS vascular type (or type IV) is a more serious form, characterized by a predisposition to vascular and digestive ruptures, increasing the risk of premature death [10]. Other rarer variants of EDS are described in table 2.

Marfan syndrome (MFS) is an HDCT with clinical characteristics that include the ocular, skeletal (long bone overgrowth is especially striking) and cardiovascular systems. The diagnosis of MFS is made using the revised Ghent criteria [11] with a possible molecular confirmation for most patients [7]. The incidence of MFS is estimated to be 1 in 5000, affecting both sexes equally [12].

For decades, clinicians and researchers have pointed out the co-occurrence of HDCT, JH and psychiatric symptoms. For instance, an indirect reference is founded in the classical psychosomatic literature where hypotonia or low muscle tone (predominant symptom of a entity known as visceroptosis in which viscera displace below their natural position due to ligamental laxity) appears linked to psychoneurosis, phobias and anxiety states [13], [14]. Later, the rheumatologist Rotés Querol [15] indicated the remarkable degree of nervous tension shown by hypermobile patients. Lumley et al. [16] observed in a sample of 48 patients with EDS that over 70% had a history of some mental health use. Van Den Bossche et al. [17], in turn, suggested that psychiatric symptoms may be part of the clinical phenotype of MFS.

No review exists to document current knowledge that associates the JH and HDCTs to the psychiatric field. In this sense, the aim of the present work is provide an overview of psychiatric conditions linked to JH and HDCTs (JHS, EDS, and MFS).

Section snippets

Method

The present narrative review is based upon a comprehensive search conducted in scientific online databases (Medline, PsychInfo) encompassing publications based on quantitative and qualitative research, including case reports. Published books and papers found by hand-searching references have also been used. Our search included studies published from 1950 until May 2014, without exclusion of the language of publication. The selection was made using the following terms : “hypermobility,” “Marfan

Results

One hundred and two articles were included in this review. The information was regrouped according to the category of mental problems for which some evidence of association referring to HDCT or JH was found. These are anxiety disorders, depression, schizophrenia, neurodevelopmental disorders, eating disorders, personality disorders and substance use/misuse. The hypotheses proposed to explain the association between JH, HDCT and these psychiatric conditions were exposed in the Discussion section.

Discussion

As has been seen, a wide range of psychiatric problems have been associated to JH and HDCT. As regards MFS and EDS, these are multisystemic disorders having, in some cases, life-threatening complications. Those affected may also experience chronic pain, disability, avoidance of relationships and social activities, sexual difficulties [16], concerns linked to transmitting the disease to progeny, teasing and stigmatizing associated with the phenotypic appearance of MFS [26], [34], and other

Conclusion

In conclusion, a wide range of psychiatric conditions have been associated with JH and HDCT; however, the evidence concerning some of these conditions (e.g., autism, schizophrenia) arises mainly from cases reports. In contrast, the link between anxiety states and JH is well established, with evidence being obtained from cross-sectional and follow-up studies. Despite the need of more research, the available data highlight the importance of exploring psychiatric symptoms in patients with HDCT

Conflict of interest

The authors declare no conflict of interest.

Funding

This study had no funding support.

References (102)

  • M. Lemberg et al.

    Marfan syndrome and schizophrenia: a case report and literature review

    Gen Hosp Psychiatry

    (2010)
  • J.C. Leone et al.

    Marfan's syndrome and neuropsychiatric symptoms: case report and literature review

    Compr Psychiatry

    (1986)
  • X. Ming et al.

    Prevalence of motor impairment in autism spectrum disorders

    Brain Dev

    (2007)
  • M. Shetreat-Klein et al.

    Abnormalities of joint mobility and gait in children with autism spectrum disorders

    Brain Dev

    (2014)
  • D. Tantam et al.

    Asperger's syndrome and ligamentous laxity

    J Am Acad Child Adolesc Psychiatry

    (1990)
  • K.G. Sieg

    Autism and Ehlers Danlos syndrome

    J Am Acad Child Adolesc Psychiatry

    (1992)
  • A.S. Kaplan et al.

    Eating disorders and connective tissue disease. Etiologic and treatment considerations

    Psychosomatics

    (1992)
  • F. Stramesi et al.

    Marfan syndrome and liability to psychosis

    Med Hypotheses

    (2007)
  • L.N. Cupo et al.

    Ehlers–Danlos syndrome with abnormal collagen fibrils, sinus of Valsava aneurysm, myocardial infarction, panacinar emphysema and cerebral heterotopias

    Am J Med

    (1981)
  • M. Gratacòs et al.

    A polymorphic genomic duplication on human chromosome 15 is a susceptibility factor for panic and phobic disorders

    Cell

    (2001)
  • M. Tabiner et al.

    Failure to find DUP25 in patients with anxiety disorders, in control individuals, or in previously reported positive control cell lines

    Am J Hum Genet

    (2003)
  • H.D. Critchley et al.

    Visceral influences on brain and behavior

    Neuron

    (2013)
  • H.D. Critchley et al.

    Interaction between cognition, emotion, and the autonomic nervous system

    Handb Clin Neurol

    (2013)
  • A.J. Hakim et al.

    The heritable disorders of connective tissue: epidemiology, nosology and clinical features

  • P. Beighton et al.

    Articular mobility in an African population

    Ann Rheum Dis

    (1973)
  • R. Grahame et al.

    The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS)

    J Rheumatol

    (2000)
  • P. Beighton et al.

    Ehlers–Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers–Danlos National Foundation (USA) and Ehlers–Danlos Support Group (UK)

    Am J Med Genet

    (1998)
  • B.T. Tinkle et al.

    The lack of clinical distinction between the hypermobility type of Ehlers–Danlos syndrome and the joint hypermobility syndrome (a.k.a. hypermobility syndrome)

    Am J Med Genet A

    (2009)
  • M. Pepin et al.

    Clinical and genetic features of Ehlers–Danlos syndrome type IV, the vascular type

    N Engl J Med

    (2000)
  • B.L. Loeys et al.

    The revised Ghent nosology for the Marfan syndrome

    J Med Genet

    (2010)
  • R. Pyeritz

    Marfan syndrome and other disorders of fibrillin

  • H. Flanders

    Diagnostico y tratamiento psicosomaticos

    (1950)
  • A. Bulbena et al.

    Somatic conditions intrinsic to anxiety disorders

  • J. Rotés et al.

    La laxitud articular como factor de alteraciones del aparato locomotor

    Rev Esp Reumatol

    (1957)
  • M.A. Lumley et al.

    Psychosocial functioning in the Ehlers–Danlos syndrome

    Am J Med Genet

    (1994)
  • G. Pailhez et al.

    Co-morbid anxiety and physical disorders: a possible common link with joint hypermobility syndrome

  • R. Martín-Santos et al.

    Association between the joint hypermobility syndrome and panic disorder

    Am J Psychiatry

    (1998)
  • C. Baeza-Velasco et al.

    Association between psychopathological factors and joint hypermobility syndrome in a group of undergraduates from a French university

    Int J Psychiatry Med

    (2011)
  • T.O. Smith et al.

    The relationship between bening joint hypermobility syndrome and psychological distress: a systematic review and meta-analyses

    Rheumatology

    (2014)
  • A. Van Tongerloo et al.

    Psychosocial adaptation in adolescents and young adults with Marfan syndrome: an exploratory study

    J Med Genet

    (1998)
  • C. Baeza-Velasco et al.

    Ansiedad social y alteracion de colageno en personas de gran estatura

    Cuad Psicosom Psiquiatr Enlace

    (2009)
  • G. Gurer et al.

    The anxiety between individuals with and without joint hypermobility

    Eur J Psychiatry

    (2010)
  • M. Pasquini et al.

    Unexpected association between joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type and obsessive-compulsive personality disorder

    Rheumatol Int

    (2014)
  • R. Martín-Santos

    Trastorno por Ansiedad y Laxitud Articular: más allá de la coincidencia

    (1992)
  • B. Murray et al.

    Ehlers–Danlos syndrome, hypermobility type: a characterization of the patients' lived experience

    Am J Med Genet

    (2013)
  • G. Mercuro et al.

    Association between psychiatric disorders and Marfan's syndrome in a large Sardinian family with a high prevalence of cardiac abnormalities

    Clin Cardiol

    (1997)
  • L. Wanson et al.

    Psychiatric symptoms and Marfan: part of the syndrome or incidental to it?

    World J Biol Psychiatry

    (2002)
  • K.F. Peters et al.

    Living with Marfan syndrome I. Perceptions of the condition

    Clin Genet

    (2001)
  • L. Cartellieri et al.

    Neurological disorders in Marfan syndrome

    Nervenarzt

    (1953)
  • P. Sirota et al.

    Schizophrenia and Marfan syndrome

    Br J Psychiatry

    (1990)
  • Cited by (0)

    View full text