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