title: Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers-Danlos syndrome from benign joint hypermobility syndrome in patients.
abstract: There is a clinical overlap between classic Ehlers-Danlos syndrome (cEDS) and benign joint hypermobility syndrome (BJHS), with hypermobility as the main symptom. The purpose of this study was to investigate the role of type V collagen mutations and tendon pathology in these 2 syndromes. In patients (cEDS, n=7; BJHS, n=8) and controls (Ctrl, n=8), we measured patellar tendon ultrastructure (transmission electron microscopy), dimensions (magnetic resonance imaging), and biomechanical properties (force and ultrasonographic measurements during a ramped isometric knee extension). Mutation analyses (COL5A1 and COL5A2) were performed in the patients. COL5A1 mutations were found in 3 of 4 of the patients with cEDS. Patellar tendon dimensions were similar between the groups, but large, irregular collagen fibrils were in 4 of 5 patients with cEDS. In the cEDS group, tendon stiffness and Young's modulus were reduced to ∼50% of that in BJHS and Ctrl groups (P<0.05). The nonhypermobile, healthy controls were matched with the patients in age, sex, body weight, and physical activity, to compare outcomes. COL5A1 mutations led to structural tendon pathology and low tendon stiffness in cEDS, explaining the patients' hypermobility, whereas no tendon pathology was found that explained the hypermobility in BJHS.
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery, and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; rieharboenielsen@gmail.com.
authors.forename: Rie Harboe
authors.initials: RH
authors.lastname: Nielsen
authors.affiliation: Musculoskeletal Rehabilitation Research Unit, Department of Physical Therapy, Bispebjerg Hospital, Copenhagen, Denmark;
authors.forename: Christian
authors.initials: C
authors.lastname: Couppé
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery, and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Jacob Kildevang
authors.initials: JK
authors.lastname: Jensen
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery, and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Morten Raun
authors.initials: MR
authors.lastname: Olsen
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery, and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Katja Maria
authors.initials: KM
authors.lastname: Heinemeier
authors.affiliation: Centre for Medical Genetics, University Hospital, Ghent, Belgium; and.
authors.forename: Fransiska
authors.initials: F
authors.lastname: Malfait
authors.affiliation: Centre for Medical Genetics, University Hospital, Ghent, Belgium; and.
authors.forename: Sofie
authors.initials: S
authors.lastname: Symoens
authors.affiliation: Centre for Medical Genetics, University Hospital, Ghent, Belgium; and.
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery, and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.affiliation: Musculoskeletal Rehabilitation Research Unit, Department of Physical Therapy, Bispebjerg Hospital, Copenhagen, Denmark;
authors.forename: Stig Peter
authors.initials: SP
authors.lastname: Magnusson
authors.affiliation: Department of Rheumatology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Remvig
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery, and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Michael
authors.initials: M
authors.lastname: Kjaer
mesh_terms: D000328:Adult; D000368:Aged; D024062:Collagen Type V / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007593:Joint Instability / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D013710:Tendons / Q000503:physiopathology*; D055815:Young Adult
chemical_list: C530725:COL5A1 protein, human; D024062:Collagen Type V
keywords: cauliflower fibrils; muscle; null-allele analysis