PMID- 37499181
OWN - NLM
STAT- MEDLINE
DCOM- 20230911
LR  - 20231003
IS  - 1708-8283 (Electronic)
IS  - 0883-0738 (Print)
IS  - 0883-0738 (Linking)
VI  - 38
IP  - 8-9
DP  - 2023 Aug
TI  - Exploration of Gross Motor Function in Aicardi-Goutieres Syndrome.
PG  - 518-527
LID - 10.1177/08830738231188753 [doi]
AB  - Background: Aicardi-Goutieres syndrome (AGS) is a rare genetic disorder 
      characterized by a spectrum of motor abilities. While the Aicardi-Goutieres 
      syndrome severity score favors severely impacted individuals, there is an unmet 
      need to define tools measuring function across the Aicardi-Goutieres syndrome 
      spectrum as potential outcome assessments for future clinical trials. Methods: 
      Gross Motor Function Measure-88 (GMFM-88) and AGS Severity Scale were 
      administered in individuals affected by Aicardi-Goutieres syndrome (n = 71). We 
      characterized the performance variability by genotype. Derived versions of the 
      GMFM-88, including the GMFM-66, GMFM-66 item set (GMFM-66IS), and GMFM-66 
      Basal&Ceiling (GMFM-66BC) were calculated. The Aicardi-Goutieres syndrome cohort 
      was divided into severe (AGS Severity Scale score <4) or attenuated (>/=4). 
      Performance on the AGS Severity Scale highly correlated with total GMFM-88 scores 
      (Spearman Correlation: R = 0.91). To assess variability of the GMFM-88 within 
      genotypic subcohorts, interquartile ranges (IQRs) were compared. Results: GMFM-88 
      performance in the TREX1 cohort had least variability while the SAMHD1 cohort had 
      the largest IQR (4.23 vs 81.8). Floor effect was prominent, with most evaluations 
      scoring below 20% (n = 46, 64.79%), particularly in TREX1- and RNASEH2-cohorts. 
      Performance by the GMFM-66, GMFM-66IS, and GMFM-66BC highly correlated with the 
      full GMFM-88. The Aicardi-Goutieres syndrome population represents a broad range 
      of gross motor skills. Conclusions: This work identified the GMFM-88 as a 
      potential clinical outcome assessment in subsets of the Aicardi-Goutieres 
      syndrome population but underscores the need for additional validation of outcome 
      measures reflective of the diverse gross motor function observed in this 
      population, including low motor function. When time is limited by resources or 
      patient endurance, shorter versions of the GMFM-88 may be a reasonable 
      alternative.
FAU - Gavazzi, Francesco
AU  - Gavazzi F
AUID- ORCID: 0000-0002-4908-8395
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
AD  - Department of Molecular and Translational Medicine, University of Brescia, 
      Brescia, Italy.
FAU - Glanzman, Allan M
AU  - Glanzman AM
AD  - Department of Physical Therapy, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA.
FAU - Woidill, Sarah
AU  - Woidill S
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Formanowski, Brielle
AU  - Formanowski B
AD  - Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Dixit, Agrani
AU  - Dixit A
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Isaacs, David
AU  - Isaacs D
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Kornafel, Tracy
AU  - Kornafel T
AD  - Department of Physical Therapy, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA.
FAU - Ballance, Elizabeth
AU  - Ballance E
AUID- ORCID: 0000-0002-6742-6992
AD  - Department of Physical Therapy, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA.
FAU - Pierce, Samuel R
AU  - Pierce SR
AD  - Department of Physical Therapy, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA.
FAU - Modesti, Nicholson
AU  - Modesti N
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Barcelos, Isabella
AU  - Barcelos I
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Cusack, Stacy V
AU  - Cusack SV
AD  - Department of Occupational Therapy, Children's Hospital of Philadelphia, 
      Philadelphia, PA, USA.
FAU - Jan, Amanda K
AU  - Jan AK
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Flores, Zaida
AU  - Flores Z
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Sherbini, Omar
AU  - Sherbini O
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Vincent, Ariel
AU  - Vincent A
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - D'Aiello, Russell
AU  - D'Aiello R
AD  - Department of Biomedical & Health Informatics, Children's Hospital of 
      Philadelphia, Philadelphia, PA, USA.
FAU - Lorch, Scott A
AU  - Lorch SA
AD  - Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - DeMauro, Sara B
AU  - DeMauro SB
AD  - Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Jawad, Abbas
AU  - Jawad A
AD  - Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
FAU - Vanderver, Adeline
AU  - Vanderver A
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
AD  - Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 
      Philadelphia, PA, USA.
FAU - Adang, Laura
AU  - Adang L
AD  - Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 
      USA.
AD  - Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 
      Philadelphia, PA, USA.
LA  - eng
GR  - K23 NS114113/NS/NINDS NIH HHS/United States
GR  - U01 NS106845/NS/NINDS NIH HHS/United States
GR  - U54 NS115052/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230727
PL  - United States
TA  - J Child Neurol
JT  - Journal of child neurology
JID - 8606714
RN  - Aicardi-Goutieres syndrome
SB  - IM
MH  - Humans
MH  - *Nervous System Malformations/genetics
MH  - *Autoimmune Diseases of the Nervous System/genetics
MH  - Genotype
MH  - Mutation
PMC - PMC10530058
MID - NIHMS1914738
OTO - NOTNLM
OT  - Aicardi-Goutieres syndrome
OT  - GMFM-88
OT  - gross motor function
OT  - outcome measures
COIS- Conflicts of interest: AV receives grant and in-kind support for research from 
      Eli Lilly, Gilead, Takeda, Illumina, Biogen, Homology, Ionis, Passage Bio, 
      Orchard Therapeutics. AV serves on the scientific advisory boards of the European 
      Leukodystrophy Association and the United Leukodystrophy Foundation, as well as 
      in an unpaid capacity for Takeda, Ionis, Biogen and Illumina. LA is a consultant 
      for Takeda, Biogen, and Orchard Therapeutics. The AGS scale is copyrighted by the 
      Children's Hospital of Philadelphia.
EDAT- 2023/07/27 19:10
MHDA- 2023/09/11 06:42
PMCR- 2023/09/27
CRDT- 2023/07/27 16:03
PHST- 2023/09/11 06:42 [medline]
PHST- 2023/07/27 19:10 [pubmed]
PHST- 2023/07/27 16:03 [entrez]
PHST- 2023/09/27 00:00 [pmc-release]
AID - 10.1177/08830738231188753 [doi]
PST - ppublish
SO  - J Child Neurol. 2023 Aug;38(8-9):518-527. doi: 10.1177/08830738231188753. Epub 
      2023 Jul 27.