Table 1 Review papers including disease, author, study type, sample age and size, outcome measures and main findings

CMT

Cross-sectional, observational

Estilow et al. 2019 [13]

CMT n = 520

10.9 (4.4)

Balance (BOT-2)

↓ balance

Mean (SD)

z-score − 3.25 (2.9)

Cross-sectional, case-controlled observational Kennedy et al. 2019 [14]

CMT n = 50

TD n = 50

CMT 12.5 (3.9)

TD 12.5 (3.9)

6MWT

Balance (BOT-2)Walk-12

↓ 6MWD

CMT 507.7 (137.3)

TD 643.3 (75.6);

p < 0.001

Norm to height

CMT 341.9 (95.7)

TD 429.4 (56.0);

p < 0.001

↓ balance (BOT-2 /37) median (IQR)

CMT 19 (9)

TD 32 (3)

p < 0.001

Walk-12 mean score 24.7% (SD 19) 95% CI [19.3, 30.2]

n = 49

Longitudinal observational Baptista et al. 2019 [15]

CMT n = 40

TD n = 49

CMT 11.45 (3.50)

TD 10.62 (3.10)

10 m walk test

(baseline)

Slower 10 m walk

Median (25th; 75th)

CMT 7.90 (6.67;8.92)

TD 7.25 (5.60; 8.56);

p ≤ 0.05

Cross-sectional, case-controlled observational Kennedy et al. 2018 [11] ^b1

CMT n = 30

TD n = 30

CMT 11.5 (3.7)

TD 11.5 (3.7)

Gait speed

6MWT

10 m walk/run (n = 26)

Balance (BOT-2)

Slower speed

CMT 1.19 (0.16)

TD 1.32 (0.14);

p < 0.001

↓ 6MWD

CMT 557 (73)

TD 615 (71);

p < 0.001

Slower 10 m walk/run

CMT 3.8 (1.0)

TD 2.9 (0.3);

p < 0.001

↓ balance (BOT-2 /37) Median (IQR)

CMT 25.5 (4–34)

TD 32 (26–35)

p < 0.001

Longitudinal cohort Kennedy et al. 2017 [16] ^b1

CMT n = 27

Baseline 11.1 (3.7)

12 months 12.2 (3.7)

Gait speed non−/norm

6MWT non−/norm

Balance (BOT-2)

Functional mobility scale (FMS)

Slower norm speed over 12 months

Baseline 1.18 (0.16)

12 months 1.15 (0.14);

p = 0.22

Baseline 0.43 (0.07)

12 months 0.41 (0.05); p = 0.04

↓ norm 6MWD over 12 months

Baseline 556 (73.7)

12 months 555 (80.2);

p = 0.91

Baseline 720 (117)

12 months 690 (121); p = 0.006

No change in balance over 12 months (BOT-2 /37)

Baseline 22.6 (9.4)

12 months 23.3 (8.7)

p = 0.76

FMS 78% reported reduced ambulatory function

Cross-sectional, observational cohort

Cornett et al. (2016) [17]

CMT n = 520

10.9 (4.4)

6MWT

↓ 6MWD in CMT genotypes

6MWD z-scores reduced in CMT2A, CMT1B, CMT4C compared with CMT1A and CMTX1;

p < 0.05

6MWD z-scores reduced in CMT2A and CMT4C compared with CMT1B; p < 0.05

Systematic review

Kennedy et al. (2016) [18]

7 eligible studies

Mean 13

Range 2–52

Gait speed

Slower speed

Range 0.50–1.25

Cross-sectional, observational

Ounpuu et al. (2013) [19]

CMT n = 33

TD database

CMT 11.9 (3.6)

TD 12.0 (3.0)

Gait speed

Slower speed dependent on gait dysfunction

CMT toe walker 1.17 [0.21]

CMT “typical” 1.11 [0.16]^a

CMT foot drop 1.03 [0.21]^a

TD control 1.27 [0.11];

p < 0.001 ^a compared with TD

Longitudinal Ferrarin et al. (2013) [20] ^b2

CMT n = 16

13.2 (2.9)

Gait speed

Non-significant changes in speed with large inter-subject variability

Cross-sectional, case-controlled observational

Ferrarin et al. (2012) [21] ^b2

CMT n = 21

TD n = 18

CMT 11.9 (2.8) yo

TD 11.0 (3.3) yo

Gait speed

Slower norm speed

CMT1A foot drop and push-off deficit 69 [9]

TD 77 [7];

p < 0.05

Norm to height

Cross-sectional observational

Pagliano et al. (2011) [22]

n = 21

11.9 (2.8) range 6–17

Walk-12

Walk-12

Mean 12.4% (SD 9.5) Range 0–33

RCT

Rose et al. (2010) [23] ^a

CMT treatment group n = 15

CMT placebo group n = 15

CMT treatment 10 [4] yo

CMT placebo 11 [3] yo

Gait speed

CMT treatment group 0.50 [0.10]

CMT placebo group

0.60 [0.50]

RCT

Burns et al. (2009a) [24] ^b3

n = 81

[n = 53 for gait data; n = 65 for 6MWT data]

8.3 (3.5)

Gait speed

6MWT

Baseline

CMT treatment group 1.19 (0.16)

CMT placebo group 1.24 (0.19)

Baseline

CMT treatment group 519 (86)

CMT placebo group

521 (98)

Cross-sectional, observational

Burns et al. (2009b) [25] ^b3

n = 81

[n = 53 for gait data; n = 65 for 6MWT data]

8.3 (3.5)

Gait speed

6MWT

CMT 2–6 yo 1.13 (0.25)

CMT 7–11 yo 1.25 (0.12)

CMT 12–16 yo 1.23 (0.14)

CMT 2–6 yo 494.3 (70.6) 385–640

CMT 7–11 yo 526.8 (83.1) 250–640

CMT 12–16 yo 518.7 (150.2) 110–710

Cross-sectional, observational

Newman et al. (2007) [26] ^a

n = 16

TD database n = 40

CMT 20.1 (13)

TD 18.4 (8.5)

Gait speed

Slower speed

CMT 1.12 (0.17)

TD controls 1.31 (0.13);

p < 0.001

DMD

Longitudinal

Fowler et al. (2018) [27]

n = 42

7.9 (2.9)

Range 4.1–16.1

10 m walk/run test

StepWatch Activity monitoring

Baseline speed 1.71 (0.68) m/s as measured by 10 m walk/run

Baseline 5.85 s derived from reported gait speed

Significant ↓ average strides per day with ↑ age; per age group average strides per day ↑ for 4-7yo, plateau for 8-10yo and ↓ >10yo

Systematic review of gait

Goudriaan et al. (2018) [28]

9 eligible studies

Gait speed calculated from 6 studies

Slower speed compared to TD

Standardised mean difference (effect size) ranging from 1.26 to 3.20

RCT

Victor et al. (2017) [29]

n = 331

9.6 (1.92)

6MWT

10 m walk/run

Baseline

329.6 (55.47)

Baseline

6.8 (1.97)

Cross-sectional observational

case controlled

Alfano et al. (2017) [30]

DMD n = 72

TD n = 599

DMD range 4–12

TD range 4–14

100 m timed test

Slower timed 100 m across all ages compared to TD; p < 0.01

DMD times improve up to 6 years and then decline from 7 years

Cross-sectional, observational case controlled

Ropars et al. (2016) [31]

DMD n = 16

TD n = 15

DMD 8.67 (2.04)

TD 9.39 (2.21)

Gait speed

Slower speed compared to TD

DMD 0.78 (0.18)

TD 1.21 (0.13);

p < 0.001

Cross-sectional observational case-controlled

Davidson et al. (2015) [32]

DMD n = 16

TD n = 13

DMD 9.0 (2.1)

TD 9.0 (2.4)

6MWT

StepWatch Activity monitoring

↓ 6MWD compared to TD

DMD 387 (86)

TD 598 (63);

p < 0.005

↓ steps and high activity time and ↑ inactive time compared to TD

Steps

DMD 5138 (2500)

TD 7239 (2621);

p = 0.044

High activity time

DMD 25 (17)

TD 53 (34) min

p = 0.018

Inactive time

DMD 1103 (134) min

TD 1016 [33] min;

p = 0.036

Longitudinal observational

Pane et al. (2014) [34] ^b4

n = 96

Baseline

8.3 (2.3)

6MWT

↓ 6MWD 3 years

− 15.8 (77.3) at 12 months, − 58.9 (125.7) at 24 months and − 104.22 (146.2) at 36 months

Longitudinal observational

Mazzone et al. (2013) [35] ^b4

n = 113

8.2

4.1–17.0

6MWT

↓ 6MWD 2 years

− 22.7 (SD 81.0) 1st year − 64.7 (SD 123.1) 2nd year

Longitudinal observational

Henricson et al. (2013a) [36]

n = 340

Baseline range

2–28

10 m walk/run

Slower 10 m walk/run with ↑ age

No participant aged > 18 years able to walk

Longitudinal observational, case-controlled

Henricson et al. (2013b) [37]

DMD n = 24

TD n = 36

1 year

DMD n = 13

TD n = 18

DMD 7.9 (2.3)

TD 8.7 (2.6)

6MWT

10 m walk/run

Baseline ↓ 6MWD

DMD 369.5 (79.3)

TD 613.3 (73.6) p < 0.001

MCID 26.4 m

1 year change DMD > MCID

DMD − 53.67 (SE 25.96) p = 0.027

TD 16.5 (SE 11.46)

Baseline ↓time

DMD 1.68 (0.56)

TD 3.32 (0.36)

p < 0.001

MCID 0.19 s

1 year change DMD > MCID

DMD − 0.25 (SE 0.68) p = 0.007

TD 0.33 (SE 0.07) p < 0.001

Observational study McDonald et al. (2013a) [38]

n = 174

8.5 (2.6)

6MWT

10 m walk/run

358 (95)

MCID 28.5–31.7 m

7.4 (4.3)

MCID 2.3–1.4 s

Longitudinal observational study

McDonald et al. (2013b) [39]

n = 57

8.3 (2.33)

6MWT

10 m walk/run

↓ 6MWD 48 weeks

Baseline 361.1 (87.5)

Week 48,317.4 (152.3)

Slower 10 m walk/run with ↑ age

Baseline

< 7yo 4.8 (0.86)

> 7yo 7.1 (2.80)

Longitudinal observational study

Bello et al. (2012) [40]

n = 80

2 genotypes

Group 1 = 57

Group 2 = 23

8.3 (2.7)

6MWT

↓ 6MWD 12 months, associated with age (r = − 0.38 p = 0.013), baseline 6MWD (r = 0.73, p < 0.001) and genotype (p = 0.029)

Baseline

Gp 1368 (86)

Gp 2387 (67)

12 months

Gp 1360 (98)

Gp 2343 (124)

Cross-sectional, observational case controlled

Doglio et al. (2011) [41]

DMD n = 15

TD n = 9

DMD 6.1 (0.7)

TD 7.5 (1.2)

Gait speed

10 m walk

Speed in younger boys with DMD does not differ to TD

DMD 1.06 (0.17)

TD 1.07 (0.18)

NS

Slower 10 m walk

DMD 4.4 (3.2)

TD 3.4 (0.6)

p < 0.05

Longitudinal observational study

Mazzone et al. (2011) [42] ^b4

n = 106

(n = 100 10 m walk/run)

Baseline

8.3 (2.3)

10 m walk/run

6MWT

↓ 6MWD 12 months, > in older boys

≤ 7 yo − 7.8 (63.9)

> 7 yo − 42.3 (73.9)

All − 25.8 (74.3);

p = 0.01

(≤7yo vs > 7yo)

Slower 10 m walk/run in older boys

≤ 7 yo 0.3 (3.1)

> 7 yo 1.3 (3.5)

All 1.0 (3.4)

p = 0.11 ≤ 7yo vs >7yo

Cross-sectional observational study

Mazzone et al. (2010) [43]

n = 112

8.18 (2.3)

10 m walk/run

6MWT

Range 127–560.6

Range 3–15

Cross-sectional observational case controlled

McDonald et al. (2010) [44]

DMD n = 21

TD n = 34

Median [range]

DMD 8 [5–12]

TD 9 [4–12]

6MWT

↓ 6MWD compared to TD

DMD 366 (83)

TD 621 (68);

p < 0.001

Cross-sectional observational case controlled

Gaudreault et al. (2010) [8]

DMD n = 11

TD n = 14

DMD 9.2 (2.6)

TD 9.7 (1.9)

Gait speed

Slower speed

DMD 0.62 (0.12)

TD 1.02 (0.13)

p < 0.001

Cross-sectional, observational case controlled

D’Angelo et al. (2009) [45]

DMD n = 21

TD n = 10

DMD 7.0 (2.4)

TD 7.4 (1.2)

Gait speed

Trend to slower norm speed

DMD 0.81 (0.14)

TD 0.90 (0.13)

norm to height; NS

RCT

Skura et al. (2008) [46]

n = 15

Baseline

8.4 (1.46)

30 ft timed walk/run test

Baseline 30 ft timed run

5.6 (1.3)

RCT

Beenakker et al. (2005) [47]

n = 16

Baseline

6.25 (0.93)

Range 5–8

9 m run

Baseline speed 1.78 m/s

= 5.06 s over 9 m

SMA

Pilot study

Bartels et al. (2019) [48]

n = 4

26.2; range 10–37

Endurance shuttle walk test (ESWT)

ESWT feasible measure of fatigability during walking in SMA3

Longitudinal, observational

Montes et al. (2018) [10]

n = 73

13.5 (12.4) range 2.6–49.1

6MWT

Baseline SMA3a 257.1 (107.3)

SMA3b 390.2 (144.0)

Mean rate of change − 7.8 m/year; p = 0.009

Age affects rate of change

<  6 yrs.: 9.8 m/ year; 6–10 yrs.: − 7.9 m/year; 11–19 yrs.: − 20.8 m/year; > 20 yres: − 9.7 m/year; p = 0.005

Cross-sectional, observational

Montes et al. (2014) [49]

n = 10

31.2; range, 9–49

6MWT

273.4 (45.7); range, 53–492

Dunaway et al. (2014) [50]

n = 15

28.7; range 10–49

10 m walk/run

6MWT

Timed up and go (TUG)

362.13 (29.22)

7.44 (0.84)

TUG

12.97 (2.49) s;

Moderate to good correlation between TUG and 10 m walk/run (r = 0.691; p = 0.009) and 6MWT (r = − 0.514; p < 0.05)

Longitudinal observational study

Mazzone et al. (2013) [51]^a

n = 38

14.07 (12.43) 3.4–49.3

6MWT

No change in 6MWD 12 months

Baseline 294.91 (127)

12 months 293.4 (141)

Cross-sectional, case controlled

Montes et al. (2011) [9]

SMA3 n = 9

TD n = 9

22

4–49 years

6MWT

↓ 6MWD

SMA3 343 m (range 267–449)

TD 601 m (range 490–733)

Cross-sectional observational

Montes et al. (2010) [52]

n = 18

15.3(13.3)

6MWT

10 m walk/run

288.9 (161.9)

Strong correlation between 6MWT and 10 m walk/run (r = − 0.87; p < 0.0001)

Median (25th, 75th %)

8.4 (5.4,10.7)

CMD

Cross-sectional observational

Hayes et al. (2018) [53]

n = 25

7.76 (3.02) 3.25–13.22

10 m self-selected walk speed

6MWT

StepWatch activity monitoring

0.97 (0.26) 0.52–1.36

325.23 (109.85)

150–604

↓ physical activity

Time inactive, % 80.85 (9.15) Low steps, % 33.19 (13.11) Medium steps, % 51.15 (9.80) High steps, % 16.01 (10.27)

Cross-sectional observational case-controlled

Johnson et al. (2016) [54]

CMD n = 41

(6MWT n = 33)

TD n = 29

CMD 6.8 (3.3)

TD 9.1 (3.1)

6MWT

↓ 6MWD

CMD 258.3 m (SD 176)

TD 568.3 m (SD 73.2);

p < 0.001

FSHD

Observational test-retest reliability study

Eichinger et al. (2017) [55]^a

n = 86

49.1 (15.2) 18–84

6MWT

404.3 (123.9); Reliability ICC = 0.99 (n = 25)

Minimal detectable change (MDC95) 34.3

Late onset Pompe

Observational cross-sectional

McIntosh et al. (2015) [56]^a

n = 22

Gender age-matched reference data

48.6 (range 13–72)

Gait speed

6MWT

10 m fast walk test

1.02 (0.30)

Variable performance ranging from 39.4 to 110% predicted

10 m fast walk

1.41 (0.42) m/s = 7.09 s

Collagen VI

Longitudinal observational

Meilleur et al. (2015) [57]^a

n = 32

(n = 11 for 10 m walk/run and 6MWT)

Range 4.8–21.2

6MWT

10 m walk/run

338.27 (126.65) 144–600

10 m walk

8.6 (3.5) 4.0–15.8

NMD

(mixed)

Cross-sectional observational

Witherspoon et al. (2019) [58] ^c

n = 77

10.1 ± 2.93

6MWT

2MWT

442.1 (121.6)

2MWD = 149.8 (40.3) m

Strong correlation 2MWD and 6MWD

r = 0.90, p < 0.01

Cross-sectional observational

Kaya et al. (2015) [59]

n = 40

DMD = 20

PN ^d = 20

DMD 9.05 (3.1)

PN 12.95 (3.3)

6MWT

TUG

DMD 349.70 (77.18)

PN 358.85 (75.07)

NS

TUG

DMD 7.79 (1.54) s

PN 10.13 (2.63) s

p < 0.01

Cross-sectional observational

Montes et al. (2013) [60] ^{a e}

n = 114

21.3 (range 4–64)

6MWT

(% predicted of normative reference data)

Mean 61.9%

DMD/BMD 65.1%

SMA 52.0%

myasthenia gravis 66.3%

GLUT1 deficiency/mitochondrial disorders 63.9%

Cross-sectional observational

Holtebekk (2013) [61] ^f

n = 17

Median (IQR) 14.2 (3.6)

6MWT

Activity monitoring SenseWear Armband

Median (IQR) 485 (131)

Activity monitor

Moderate physical activity

Median (IQR) 2.4 (1.9) hours/weekday

1.1 (3.3) hours/weekend day