{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:34:03Z","timestamp":1790973243138,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T00:00:00Z","timestamp":1237420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Ehlers\u2013Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Muscle involvement is plausible based on recently discovered interactions between muscle cells and extracellular matrix molecules; however, muscle symptoms are only sporadically reported. We designed a cross\u2010sectional study to find out whether neuromuscular features are part of EDS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Standardized questionnaires, physical examination, nerve conduction studies, electromyography, muscle ultrasound, and muscle biopsy were performed in 40 EDS patients with the vascular, classic, tenascin\u2010X (TNX)\u2013deficient type EDS, and hypermobility type of EDS caused by <jats:italic>TNXB<\/jats:italic> haploinsufficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Muscle weakness, myalgia, and easy fatigability were reported by the majority of patients. Mild\u2010to\u2010moderate muscle weakness (85%) and reduction of vibration sense (60%) were common. Nerve conduction studies demonstrated axonal polyneuropathy in five patients (13%). Needle electromyography myopathic features in nine patients (26%) and a mixed neurogenic\u2010myopathic pattern in most (60%). Muscle ultrasound showed increased echo\u2010intensity (48%) and atrophy (50%). Mild myopathic features were seen on muscle biopsy of five patients (28%). Overall, patients with the hypermobility type EDS caused by <jats:italic>TNXB<\/jats:italic> haploinsufficiency were least affected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Mild\u2010to\u2010moderate neuromuscular involvement is common in various types of EDS, with a remarkable relation between residual TNX level and degree of neuromuscular involvement, compatible with a dose\u2013effect relation. The findings of this study should increase awareness of neuromuscular symptoms in EDS patients and improve clinical care. They also point to a role of the extracellular matrix in muscle and peripheral nerve function. This is an updated version of this article that originally published online on June 29, 2009. Ann Neurol 2009;65:687\u2013697<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.21643","type":"journal-article","created":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T13:44:55Z","timestamp":1237470295000},"page":"687-697","source":"Crossref","is-referenced-by-count":147,"title":["Neuromuscular involvement in various types of Ehlers\u2013Danlos syndrome"],"prefix":"10.1002","volume":"65","author":[{"given":"Nicol C.","family":"Voermans","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nens","family":"van Alfen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Pillen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lammens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost","family":"Schalkwijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machiel J.","family":"Zwarts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris A.","family":"van Rooij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben C. J.","family":"Hamel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baziel G.","family":"van Engelen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,6,25]]},"reference":[{"key":"e_1_2_6_2_2","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_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471221929.ch9"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa002939"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-104"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/376564"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20488"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2008.05.017"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.8.1087"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.64.748.126"},{"key":"e_1_2_6_11_2","first-page":"444","article-title":"Muscle formation in Ehlers\u2010Danlos syndrome","volume":"62","author":"Bilkey WJ","year":"1981","journal-title":"Arch Phys Med Rehabil"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.04.004"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06534-5"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.32.5.413"},{"key":"e_1_2_6_15_2","volume-title":"Muscles Testing and Function with Posture and Pain","author":"Peterson\u2010Kendall F","year":"2005"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.54.3.244"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.65.5.743"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1959.00270040037004"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880040304"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.3109\/03790799109166684"},{"key":"e_1_2_6_21_2","first-page":"254","article-title":"Cerebral vascular accidents in patients over the age of 60. III. Diagnosis and treatment","volume":"2","author":"Rankin J","year":"1957","journal-title":"Scott Med J"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.19.5.604"},{"key":"e_1_2_6_23_2","first-page":"1566","article-title":"Guideline on polyneuropathy","volume":"151","author":"van Doorn PA","year":"2007","journal-title":"Ned Tijdschr Geneeskd"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2004.09.011"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.10384"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.03.008"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2007.01228.x"},{"key":"e_1_2_6_28_2","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1002\/ajmg.a.31899","article-title":"Ehlers\u2010Danlos syndrome due to tenascin\u2010X deficiency: muscle weakness and contractures support overlap with collagen VI myopathies","volume":"143","author":"Voermans NC","year":"2007","journal-title":"Am J Med Genet A"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.48.11.953"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.71.834.245"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1989.tb02916.x"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(199807)21:7<972::AID-MUS25>3.0.CO;2-R"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(95)00003-X"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1059"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.9.1270-a"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2003.00075.x"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.11.006"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608830200"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511528200"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1086\/324123"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-005-0056-0"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1437"},{"key":"e_1_2_6_43_2","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1007\/s00401-002-0577-x","article-title":"Distribution of extracellular matrix tenascin\u2010X in sciatic nerves","volume":"104","author":"Matsumoto K","year":"2002","journal-title":"Acta Neuropathol (Berl)"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jelekin.2007.02.003"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610270104"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800962105"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21439"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0996-113"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.121027598"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30443"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2004.03.002"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000319736.43628.04"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.29.12.1620"},{"key":"e_1_2_6_54_2","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/S0196-0644(88)80570-5","article-title":"Traumatic disruption of the subclavian artery and brachial plexus in a patient with Ehlers\u2010Danlos syndrome","volume":"17","author":"Curley SA","year":"1988","journal-title":"Ann Emerg Med"},{"key":"e_1_2_6_55_2","doi-asserted-by":"crossref","first-page":"612","DOI":"10.3109\/17453679108994511","article-title":"Recurrent common peroneal palsy in association with the Ehlers\u2010Danlos syndrome. A case report","volume":"62","author":"Bell KM","year":"1991","journal-title":"Acta Orthop Scand"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.28.3.228"},{"key":"e_1_2_6_57_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30529"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.21643","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.21643","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T21:12:59Z","timestamp":1697490779000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.21643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6]]},"references-count":56,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2009,6]]}},"alternative-id":["10.1002\/ana.21643"],"URL":"https:\/\/doi.org\/10.1002\/ana.21643","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6]]}}}