{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:00:35Z","timestamp":1790776835110,"version":"4.1.0"},"reference-count":20,"publisher":"SAGE Publications","issue":"8-9","license":[{"start":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:00:00Z","timestamp":1689552000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Institute of Health","award":["U54TR002823"],"award-info":[{"award-number":["U54TR002823"]}]},{"name":"Commonwealth Universal Research Enhancement Program"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Child Neurol"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:p>TUBB4A pathogenic variants are associated with a spectrum of neurologic impairments including movement disorders and leukodystrophy. With the development of targeted therapies, there is an urgent unmet need for validated tools to measure mobility impairment. Our aim is to explore gross motor function in a pediatric-onset TUBB4A-related leukodystrophy cohort with existing gross motor outcome tools. Gross Motor Function Measure-88 (GMFM-88), Gross Motor Function Classification System (GMFCS-ER), and Gross Motor Function Classification-Metachromatic Leukodystrophy (GMFC-MLD) were selected through face validity. Subjects with a confirmed clinical and molecular diagnosis of TUBB4A-related leukodystrophy were enrolled. Participants\u2019 sex, age, genotype, and age at disease onset were collected, together with GMFM-88 and concurrent GMFCS-ER and GMFC-MLD. Performances on each measure were compared. GMFM-88 floor effect was defined as total score below 20%. A total of 35 subjects participated. Median performance by GMFM-88 was 16.24% (range 0-97.31), with 42.9% (n\u2009=\u200915) of individuals performing above the floor. GMFM-88 Dimension A (Lying and Rolling) was the best-performing dimension in the GMFM-88 (n\u2009=\u200929 above the floor). All levels of the Classification Scales were represented, with the exception of the GMFC-MLD level 0. Evaluation by GMFM-88 was strongly correlated with the Classification Scales (Spearman correlations: GMFCS-ER:GMFM-88 r\u2009=\u20090.90; GMFC-MLD:GMFM-88 r\u2009=\u20090.88; GMFCS-ER:GMFC-MLD: r\u2009=\u20090.92). Despite overall observation of a floor effect, the GMFM-88 is able to accurately capture the performance of individuals with attenuated phenotypes. GMFM-88 Dimension A shows no floor effect. GMFC-MLD shows a strong correlation with GMFCS-ER and GMFM-88, supporting its use as an age-independent functional score in TUBB4A-related leukodystrophy.<\/jats:p>","DOI":"10.1177\/08830738231188159","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T02:46:43Z","timestamp":1689648403000},"page":"498-504","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Gross Motor Function in Pediatric Onset\n                    <i>TUBB4A<\/i>\n                    -Related Leukodystrophy: GMFM-88 Performance and Validation of GMFC-MLD in\n                    <i>TUBB4A<\/i>"],"prefix":"10.1177","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4908-8395","authenticated-orcid":false,"given":"Francesco","family":"Gavazzi","sequence":"first","affiliation":[{"name":"Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virali","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Charsar","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Glanzman","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6364-0089","authenticated-orcid":false,"given":"Jacqueline","family":"Erler","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjana","family":"Sevagamoorthy","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"McKenzie","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Kornafel","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6742-6992","authenticated-orcid":false,"given":"Elizabeth","family":"Ballance","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel R.","family":"Pierce","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Teng","sequence":"additional","affiliation":[{"name":"Synaptixbio Ltd, Oxfordshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brielle","family":"Formanowski","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Woidill","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Shults","sequence":"additional","affiliation":[{"name":"Synaptixbio Ltd, Oxfordshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangeline","family":"Wassmer","sequence":"additional","affiliation":[{"name":"Neurology Department, Birmingham Children's Hospital, Institute of Health and Neurodevelopment, Aston University, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Tonduti","sequence":"additional","affiliation":[{"name":"Unit of Pediatric Neurology, COALA (Center for Diagnosis and Treatment of Leukodystrophies), V. Buzzi Children's Hospital, Milan, Italy"},{"name":"Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Magrinelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Bernard","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Neurosurgery, Pediatrics and Human Genetics, McGill University, Montreal, QC, Canada"},{"name":"Department Specialized Medicine, Division of Medical Genetics, McGill University Health Centre, Montreal, QC, Canada"},{"name":"Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo","family":"Van Der Knaap","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, Cellular & Molecular Mechanisms, Vrije Universiteit, Amsterdam, the Netherlands"},{"name":"Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, Cellular & Molecular Mechanisms, Vrije Universiteit, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Adang","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children's Hospital of 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