Gross Motor Function in Pediatric Onset TUBB4A-Related Leukodystrophy: GMFM-88 Performance and Validation of GMFC-MLD in TUBB4A

Francesco Gavazzi*, Virali Patel, Brittany Charsar, Allan Glanzman, Jacqueline Erler, Anjana Sevagamoorthy, Emma McKenzie, Tracy Kornafel, Elizabeth Ballance, Samuel R. Pierce, Michelle Teng, Brielle Formanowski, Sarah Woidill, Justine Shults, Evangeline Wassmer, Davide Tonduti, Francesca Magrinelli, Geneviève Bernard, Marjo Van Der Knaap, Nicole WolfLaura Adang, Adeline Vanderver

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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’ 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 = 15) of individuals performing above the floor. GMFM-88 Dimension A (Lying and Rolling) was the best-performing dimension in the GMFM-88 (n = 29 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 = 0.90; GMFC-MLD:GMFM-88 r = 0.88; GMFCS-ER:GMFC-MLD: r = 0.92). 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.
Original languageEnglish
Pages (from-to)498-504
Number of pages7
JournalJournal of Child Neurology
Issue number8-9
Early online date17 Jul 2023
Publication statusPublished - Aug 2023


  • GMFM-88
  • gross motor
  • leukodystrophy
  • TUBB4A
  • Severity of Illness Index
  • Reproducibility of Results
  • Humans
  • Leukodystrophy, Metachromatic/complications
  • Movement Disorders/complications
  • Tubulin/genetics
  • Cerebral Palsy
  • Motor Skills


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