Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers-Danlos syndrome from benign joint hypermobility syndrome in patients

Rie Harboe Nielsen; Christian Couppé; Jacob Kildevang Jensen; Morten Raun Olsen; Katja Maria Heinemeier; Fransiska Malfait; Sofie Symoens; Anne De Paepe; Peter Schjerling; Stig Peter Magnusson; Lars Remvig; Michael Kjær

doi:10.1096/fj.14-249656

Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers-Danlos syndrome from benign joint hypermobility syndrome in patients

Rie Harboe Nielsen, Christian Couppé, Jacob Kildevang Jensen, Morten Raun Olsen, Katja Maria Heinemeier, Fransiska Malfait, Sofie Symoens, Anne De Paepe, Peter Schjerling, Stig Peter Magnusson, Lars Remvig, Michael Kjær

29 Citations (Scopus)

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.-Nielsen, R. H., Couppé, C., Jensen, J. K., Olsen, M. R., Heinemeier, K. M., Malfait, F., Symoens, S., De Paepe, A., Schjerling, P., Magnusson, S. P., Remvig, L., Kjaer, M. Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers- Danlos syndrome from benign joint hypermobility syndrome in patients.

Original language	English
Journal	FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume	28
Issue number	11
Pages (from-to)	4668-4676
Number of pages	9
ISSN	0892-6638
DOIs	https://doi.org/10.1096/fj.14-249656
Publication status	Published - 1 Nov 2014

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Nielsen, R. H., Couppé, C., Jensen, J. K., Olsen, M. R., Heinemeier, K. M., Malfait, F., Symoens, S., De Paepe, A., Schjerling, P., Magnusson, S. P., Remvig, L., & Kjær, M. (2014). Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers-Danlos syndrome from benign joint hypermobility syndrome in patients. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 28(11), 4668-4676. https://doi.org/10.1096/fj.14-249656

Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers-Danlos syndrome from benign joint hypermobility syndrome in patients. / Nielsen, Rie Harboe; Couppé, Christian; Jensen, Jacob Kildevang et al.
In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 28, No. 11, 01.11.2014, p. 4668-4676.

Research output: Contribution to journal › Journal article › Research › peer-review

Nielsen, RH, Couppé, C, Jensen, JK, Olsen, MR, Heinemeier, KM, Malfait, F, Symoens, S, De Paepe, A, Schjerling, P , Magnusson, SP, Remvig, L & Kjær, M 2014, 'Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers-Danlos syndrome from benign joint hypermobility syndrome in patients', FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 28, no. 11, pp. 4668-4676. https://doi.org/10.1096/fj.14-249656

Nielsen RH, Couppé C, Jensen JK, Olsen MR, Heinemeier KM, Malfait F et al. Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers-Danlos syndrome from benign joint hypermobility syndrome in patients. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2014 Nov 1;28(11):4668-4676. doi: 10.1096/fj.14-249656

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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.-Nielsen, R. H., Coupp{\'e}, C., Jensen, J. K., Olsen, M. R., Heinemeier, K. M., Malfait, F., Symoens, S., De Paepe, A., Schjerling, P., Magnusson, S. P., Remvig, L., Kjaer, M. Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers- Danlos syndrome from benign joint hypermobility syndrome in patients.",

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AU - Heinemeier, Katja Maria

AU - Malfait, Fransiska

AU - Symoens, Sofie

AU - De Paepe, Anne

AU - Schjerling, Peter

AU - Magnusson, Stig Peter

AU - Remvig, Lars

AU - Kjær, Michael

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N2 - 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.-Nielsen, R. H., Couppé, C., Jensen, J. K., Olsen, M. R., Heinemeier, K. M., Malfait, F., Symoens, S., De Paepe, A., Schjerling, P., Magnusson, S. P., Remvig, L., Kjaer, M. Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers- Danlos syndrome from benign joint hypermobility syndrome in patients.

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JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology

IS - 11

ER -

Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers-Danlos syndrome from benign joint hypermobility syndrome in patients

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