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Fatigue and headache are also common, although are not yet considered diagnostic criteria. JHS\/EDS\u2010HT is a unexpectedly common condition that remains underdiagnosed by most clinicians and pain specialists. This results in interventions limited to symptomatic and non\u2010satisfactory 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\u2010writing of the natural history of JHS\/EDS\u2010HT is aimed to raise awareness among clinical geneticists and specialists treating chronic pain conditions about pain and other complications of JHS\/EDS\u2010HT. Symptoms' clustering by disease stage is proposed to investigate both the molecular causes and the symptoms management of JHS\/EDS\u2010HT in future studies. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36315","type":"journal-article","created":{"date-parts":[[2013,11,6]],"date-time":"2013-11-06T19:05:13Z","timestamp":1383764713000},"page":"2989-3004","source":"Crossref","is-referenced-by-count":143,"title":["Re\u2010writing the natural history of pain and related symptoms in the joint hypermobility syndrome\/Ehlers\u2013Danlos syndrome, hypermobility type"],"prefix":"10.1002","volume":"161","author":[{"given":"Marco","family":"Castori","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Molecular Medicine Sapienza University, San Camillo\u2010Forlanini Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Morlino","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Molecular Medicine Sapienza University, San Camillo\u2010Forlanini Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Celletti","sequence":"additional","affiliation":[{"name":"Division of Physical Therapy and Rehabilitation, Department of Orthopedic Sciences Sapienza University, Umberto I University Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Ghibellini","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics School of Pharmacy, University of North Carolina at Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Bruschini","sequence":"additional","affiliation":[{"name":"Unit of Cognitive and Behavioral Neurology, Division of Neurology and Neurophysiopathology San Camillo\u2010Forlanini Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Grammatico","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Molecular Medicine Sapienza University, San Camillo\u2010Forlanini Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Blundo","sequence":"additional","affiliation":[{"name":"Unit of Cognitive and Behavioral Neurology, Division of Neurology and Neurophysiopathology San Camillo\u2010Forlanini Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Camerota","sequence":"additional","affiliation":[{"name":"Division of Physical Therapy and Rehabilitation, Department of Orthopedic Sciences Sapienza University, Umberto I University Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh557"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2006.00873.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2006.00875.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2008.01597.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102410392606"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-009-0084-z"},{"key":"e_1_2_10_9_1","article-title":"Neuropathic pain is a common feature in Ehlers\u2013Danlos Syndrome","author":"Camerota F","year":"2013","journal-title":"J Pain Symptom Manage"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.5402\/2012\/751768"},{"key":"e_1_2_10_11_1","first-page":"13","article-title":"Joint hypermobility syndrome (a.k.a. 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