{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:38:24Z","timestamp":1763552304212,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cure SMA","award":["PG010805"],"award-info":[{"award-number":["PG010805"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The natural history of spinal muscular atrophy (SMA) is well understood, with progressive muscle weakness resulting in declines in function. The development of contractures is common and negatively impacts function. Clinically, joint hypermobility (JH) is observed but is poorly described, and its relationship with function is unknown. Methods: Lower-limb ROM (range of motion) assessments of extension and flexion at the hip, knee, and ankle were performed. ROMs exceeding the published norms were included in the analysis. The functional assessments performed included the six-minute walk test (6 MWT) and the Hammersmith Functional Motor Scale\u2014Expanded (HFMSE). Results: Of the 143 participants, 86% (n = 123) had at least one ROM measure that was hypermobile, and 22% (n = 32) had three or more. The HFMSE scores were inversely correlated with hip extension JH (r = \u22120.60, p = 0.21; n = 6) and positively correlated with knee flexion JH (r = 0.24, p = 0.02, n = 89). There was a moderate, inverse relationship between the 6 MWT distance and ankle plantar flexion JH (r = \u22120.73, p = 0.002; n = 15). Conclusions: JH was identified in nearly all participants in at least one joint in this study. Hip extension, knee flexion and ankle plantar flexion JH was associated with function. A further understanding of the trajectory of lower-limb joint ROM is needed to improve future rehabilitation strategies.<\/jats:p>","DOI":"10.3390\/jcm13092634","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T04:01:52Z","timestamp":1714449712000},"page":"2634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Beyond Contractures in Spinal Muscular Atrophy: Identifying Lower-Limb Joint Hypermobility"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0004-6960","authenticated-orcid":false,"given":"Elizabeth R.","family":"Harding","sequence":"first","affiliation":[{"name":"Department of Rehabilitation and Regenerative Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1414-6890","authenticated-orcid":false,"given":"Cara H.","family":"Kanner","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Regenerative Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Pasternak","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Physical and Occupational Therapy Services, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7145-2608","authenticated-orcid":false,"given":"Allan M.","family":"Glanzman","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9322-0608","authenticated-orcid":false,"given":"Sally","family":"Dunaway Young","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neurosciences, Stanford University, Palo Alto, CA 94304, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashwini K.","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Regenerative Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"McDermott","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY 14642, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0743-8879","authenticated-orcid":false,"given":"Zarazuela","family":"Zolkipli-Cunningham","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neurosciences, Stanford University, Palo Alto, CA 94304, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9351-7054","authenticated-orcid":false,"given":"Richard S.","family":"Finkel","sequence":"additional","affiliation":[{"name":"Center for Experimental Neurotherapeutics, Department of Pediatric Medicine, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basil T.","family":"Darras","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darryl C.","family":"De Vivo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7357-0819","authenticated-orcid":false,"given":"Jacqueline","family":"Montes","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Regenerative Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1001\/archneurol.2011.74","article-title":"Spinal muscular atrophy: A timely review","volume":"68","author":"Kolb","year":"2011","journal-title":"Arch. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1093\/hmg\/ddn156","article-title":"Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy","volume":"17","author":"Kariya","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1172\/JCI131989","article-title":"Muscle-specific SMN reduction reveals motor neuron\u2013independent disease in spinal muscular atrophy models","volume":"130","author":"Kim","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.ydbio.2011.05.667","article-title":"Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons","volume":"356","author":"Lee","year":"2011","journal-title":"Dev. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1007\/s00018-018-2849-1","article-title":"The role of survival motor neuron protein (SMN) in protein homeostasis","volume":"75","author":"Chaytow","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_6","unstructured":"Darras, B.T., Markowitz, J.A., Monani, U.R., and De Vivo, D.C. (2015). Neuromuscular Disorders of Infancy, Childhood, and Adolescence, Academic Press."},{"key":"ref_7","unstructured":"Darras, B.T., Monani, U.R., and De Vivo, D.C. (2017). Swaiman\u2019s Pediatric Neurology, Elsevier."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1001\/archneurol.2010.373","article-title":"Observational study of spinal muscular atrophy type 2 and 3: Functional outcomes over 1 year","volume":"68","author":"Kaufmann","year":"2011","journal-title":"Arch. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1086\/338627","article-title":"Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: Fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy","volume":"70","author":"Schwarzer","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1097\/PEP.0000000000000515","article-title":"Quantitative evaluation of lower extremity joint contractures in spinal muscular atrophy: Implications for motor function","volume":"30","author":"Salazar","year":"2018","journal-title":"Pediatr. Phys. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"27","DOI":"10.5604\/15093492.933792","article-title":"Contractures of the lower extremities in spinal muscular atrophy type II. Descriptive clinical study with retrospective data collection","volume":"13","author":"Fujak","year":"2011","journal-title":"Ortop. Traumatol. Rehabil."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/j.apmr.2004.01.043","article-title":"Joint range of motion limitations in children and young adults with spinal muscular atrophy","volume":"85","author":"Wang","year":"2004","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.nmd.2017.11.005","article-title":"Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care","volume":"28","author":"Mercuri","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/ajmg.c.31433","article-title":"The neuromuscular differential diagnosis of joint hypermobility","volume":"169","author":"Donkervoort","year":"2015","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/ajmg.c.31539","article-title":"A framework for the classification of joint hypermobility and related conditions","volume":"175","author":"Castori","year":"2017","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jpeds.2010.07.021","article-title":"Beighton score: A valid measure for generalized hypermobility in children","volume":"158","author":"Klerks","year":"2011","journal-title":"J. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00415-009-0105-1","article-title":"Joint hypermobility as a distinctive feature in the differential diagnosis of myopathies","volume":"256","author":"Voermans","year":"2009","journal-title":"J. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Beighton, P.H., Grahame, R., and Bird, H. (2011). Hypermobility of Joints, Springer Science & Business Media.","DOI":"10.1007\/978-1-84882-085-2"},{"key":"ref_19","unstructured":"Norkin, C.C., and White, D.J. (2016). Measurement of Joint Motion: A Guide to Goniometry, FA Davis."},{"key":"ref_20","unstructured":"American Academy of Orthopaedic Surgeons (1965). Joint Motion: Method of Measuring and Recording, Churchill Livingstone."},{"key":"ref_21","first-page":"25","article-title":"Muscles, testing and function","volume":"18","author":"Kendall","year":"1984","journal-title":"Br. J. Sport. Med."},{"key":"ref_22","unstructured":"Stanley, H. (1976). Physical Examination of the Spine and Extremities, Appleton-Century-Crofts."},{"key":"ref_23","unstructured":"Engelberg, A.L. (1988). Guides to the Evaluation of Permanent Impairment, American Medical Association Press."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1212\/WNL.0000000000003466","article-title":"Normative reference values for strength and flexibility of 1000 children and adults","volume":"88","author":"McKay","year":"2017","journal-title":"Neurology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0887-8994(93)90082-N","article-title":"Prospective study of spinal muscular atrophy before age 6 years","volume":"9","author":"Iannaccone","year":"1993","journal-title":"Pediatr. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S150","DOI":"10.1097\/00002060-199509001-00009","article-title":"Profiles of neuromuscular diseases. Spinal muscular atrophy","volume":"74","author":"Carter","year":"1995","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/PEP.0b013e31818b7994","article-title":"Intrarater range of motion reliability in cerebral palsy: A comparison of assessment methods","volume":"20","author":"Glanzman","year":"2008","journal-title":"Pediatr. Phys. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1093\/ptj\/65.9.1339","article-title":"Reliability of goniometric measurements in patients with Duchenne muscular dystrophy","volume":"65","author":"Pandya","year":"1985","journal-title":"Phys. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1097\/01.pep.0000234960.88761.97","article-title":"Within-session inter-rater realiability of goniometric measures in patients with spastic cerebral palsy","volume":"18","author":"McWhirk","year":"2006","journal-title":"Pediatr. Phys. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/mus.26633","article-title":"Nusinersen improves walking distance and reduces fatigue in later-onset spinal muscular atrophy","volume":"60","author":"Montes","year":"2019","journal-title":"Muscle Nerve"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1212\/WNL.0b013e3181d3e308","article-title":"Six-Minute Walk Test demonstrates motor fatigue in spinal muscular atrophy","volume":"74","author":"Montes","year":"2010","journal-title":"Neurology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.nmd.2007.05.009","article-title":"An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients","volume":"17","author":"Glanzman","year":"2007","journal-title":"Neuromuscul. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1093\/rheumatology\/kex043","article-title":"Beighton scores and cut-offs across the lifespan: Cross-sectional study of an Australian population","volume":"56","author":"Singh","year":"2017","journal-title":"Rheumatology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3233\/JND-200550","article-title":"Neuroanatomical Models of Muscle Strength and Relationship to Ambulatory Function in Spinal Muscular Atrophy","volume":"7","author":"Fabiano","year":"2020","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Scheper, M.C., de Vries, J.E., Juul-Kristensen, B., Nollet, F., and Engelbert, R.H. (2014). The functional consequences of Generalized Joint Hypermobility: A cross-sectional study. BMC Musculoskelet. Disord., 15.","DOI":"10.1186\/1471-2474-15-243"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1007\/s00415-019-09646-w","article-title":"MRI patterns of muscle involvement in type 2 and 3 spinal muscular atrophy patients","volume":"267","author":"Brogna","year":"2020","journal-title":"J. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/mus.24081","article-title":"Leg muscle function and fatigue during walking in spinal muscular atrophy type 3","volume":"50","author":"Montes","year":"2014","journal-title":"Muscle Nerve"},{"key":"ref_38","first-page":"113","article-title":"Proximal spinal muscular atrophy: Current orthopedic perspective","volume":"6","author":"Haaker","year":"2013","journal-title":"Appl. Clin. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1093\/rheumatology\/kem290","article-title":"Inter-examiner reproducibility of tests and criteria for generalized joint hypermobility and benign joint hypermobility syndrome","volume":"46","author":"Rogind","year":"2007","journal-title":"Rheumatology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/9\/2634\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:36:47Z","timestamp":1760107007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/9\/2634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,30]]},"references-count":39,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["jcm13092634"],"URL":"https:\/\/doi.org\/10.3390\/jcm13092634","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2024,4,30]]}}}