Stepping Activity in Children With Congenital Myotonic Dystrophy

Abstract

Purpose: 

The purpose of this study was to investigate the physical activity levels in children with congenital myotonic dystrophy (CDM), and to examine whether patient clinical and functional characteristics correlated to physical activity.

Methods: 

Twenty-five children with CDM were assessed on functional measures, clinical measures, and physical activity levels.

Results: 

Results support that children with CDM spend the majority of their time inactive. There was a negative correlation between inactivity and cytosine-thymine-guanine repeats, suggesting increased inactivity with increased CDM severity. Age, body mass index, and lean muscle mass may be factors influencing activity levels.

Conclusions: 

Children in this study received one-third the recommended steps per day. The number of steps per day is not correlated with clinical measures.

In Brief

The purpose of this study was to investigate the physical activity levels in children with congenital myotonic dystrophy and to examine whether patient clinical and functional characteristics correlated to physical activity.

INTRODUCTION

Myotonic dystrophy type-1 (DM1) is an autosomal dominant disorder caused by a cytosine-thymine-guanine (CTG_n) repeat expansion in the 3′ untranslated region of the DMPK gene.¹ DM1 demonstrates anticipation, and a CTG repeat expansion in DMPK may increase and become unstable with each generation.² The larger the CTG repeat, the greater the symptom severity. Congenital myotonic dystrophy (CDM), the most severe form of DM1, is characterized by symptom onset at birth. Children may have poor feeding, hypotonia, talipes equinovarus, and respiratory failure at birth.³ A 25% chance of mortality may occur if the child requires ventilation longer than 3 months; however, surviving infants experience gradual improvement in motor function.^3,4 While development of gross motor skills is delayed, children with CDM frequently attain motor milestones of walking, running, and stair climbing during childhood.^5,6

With development of mobility skills comes participation in physical activity, which is defined as “any bodily movement produced by skeletal muscle that results in energy expenditure.”⁷ All children, even children with a disability, benefit from physical activity, although it may be especially difficult for individuals with CDM because of body structure and function impairments as well as neonatal course.^7,8 The amount of physical activity, assessed as steps per day, time spent inactive, and time spent active, has not been characterized in children with CDM. Furthermore, it is not known whether specific patient demographics (eg, age and gender), body structure and function (eg, body mass index [BMI], CTG repeats, and lean muscle mass), mobility, and functional activity status (eg, endurance and rise from floor) may contribute to more or less participation in physical activity.

The purpose of this cross-sectional study is to investigate the physical activity levels in individuals with CDM, and to examine whether patient characteristics correlate to indicators of physical activity (total steps per day, time spent in inactivity, and time spent in high-intensity activity). Stepping activity and activity level may also be useful benchmarks for future therapeutic trials.

METHODS

Participants

Participants with CDM were recruited at University of Utah and University of Western Ontario as part of a disease progression cohort study.⁹ Informed consent was compliant with the University of Utah Institutional Review Board and included a Parental Permission Form and assent form for children older than 7 years. Consistency of data collection was ensured by protocol standardization between the 2 sites, with an in-person training conducted by the principal investigator.

Subjects with CDM between ages 0 to 13 years, 11 months were included in the disease progression study. All patients exhibited symptoms of CDM at birth including an onset of symptoms in the neonatal period requiring 72 hours or more of hospitalization, and a history of hypotonia, respiratory failure, or feeding difficulty. Genetic testing was required for inclusion, confirming an expanded CTG repeat in the DMPK gene and an expanded CTG repeat size of greater than 200 repeats. We performed a cross-sectional analysis of individuals who could walk independently with assistive devices or bracing for a minimum of 10 ft.

Study Procedures

Children were seen during an approximate 5-hour period to collect all the clinical outcomes as part of a larger study. Age, gender, body structure and function, mobility, and functional activity outcomes were collected.

Body Structure and Function

Clinical and patient characteristics included CTG repeat and total body lean muscle mass. Total body lean muscle mass, defined as right and left arm mass, and right and left leg mass were obtained using a Hologic scanner using pediatric software. Instruments were calibrated daily and values of lean mass were recorded in grams.

Mobility and Functional Activity Measures

Mobility and functional activity measures included the 6-minute walk test (6MWT), rise from floor time, and 10-m self-selected gait speed (10SS). Test data for mobility measures were not considered valid if participants refused to participate, had severe behavioral issues or autism, or were not able to understand the directions of the task.

The 6MWT is a standardized functional measure and is reliable in this population (intraclass correlation coefficient [ICC] = 0.96).^10–12 The test was performed by 2 administrators, on a 25-m course, marked with a cone at each end to walk around and with a mark for each meter. The child was asked to walk “as far as possible for 6 minutes.” Children were encouraged verbally during the task. Children were discouraged from running and were allowed to have a standing rest if needed. Total distance was recorded in meters.

The timed rise from floor test is a standardized timed function test used for children with neuromuscular disorders with good test-retest reliability (ICC = 0.97).^13,14 Children started supine on a 2-inch thick, dense foam core gym mat with arms by their side and were asked to come to a standing position with feet together and arms at their side as quickly as possible. The child was provided a demonstration and verbal explanation of the test. Time to perform the task was recorded in seconds.

The 10SS test is a measure of gait speed and has been validated (ICC = 0.91) in children with neuromuscular disorders.¹⁵ The child was asked to walk down a hallway on a 12-m course using any assistive device or bracing as needed. When the child's first foot crossed over the last 10-m mark, the time was recorded in seconds. Three trials were performed and the average was recorded and reported in speed meters/seconds.

Physical Activity Measures

Physical activity was assessed using a step activity monitor (SAM; modus StepWatch, Washington, District of Columbia) to assess walking activity during day-to-day life. The SAM has been validated in children who are developing typically¹⁶ and in children with neuromuscular disorders.¹⁷ Children were asked to wear the monitors on the right leg for 7 consecutive days (24 hours each day). They were allowed to take the device off during bathing/showering. Measures of physical activity were assessed based on the mean total steps per day, mean percent time they were inactive in a day, mean percent time of their total steps they spent in low, medium, and high activity, defined as 1 to 15 steps/minute, 16 to 39 steps/minute, and greater than 40 steps/minute, respectively, according to the parameters established by StepWatch. Data are reported as single limb only, unless otherwise noted. Only days of full data, defined as 1440 minutes, were considered for analysis.

Statistical Analysis

Data were analyzed with IBM SPSS Statistics, version 23. Demographic, body structure and function, mobility, and functional activity data are provided using point estimators. A correlational analysis, using the Pearson correlation coefficient, was performed between total steps per day, percent time in inactivity, and percent time in high activity compared with age, BMI, CTG repeat length, total lean body mass, 10SS, rise from floor time, and 6MWT. This study was part of a larger study and sample size was convenience based on the number of individuals who met the criteria for walking to be able to wear a SAM. Significance was set retrospectively at a P value of .05, with interpretation using Cohen's correlation effect size of 0.1 small, 0.3 medium, and 0.5 large effect.¹⁸

RESULTS

Twenty-five children (12 females), with a mean age of 7.76 (standard deviation [SD], 3.02; range, 3.25-13.22) years, completed all components of data collection. The device was worn on average 5.28 (SD, 1.77) days. From the 43 children in the larger study, 18 were not included in this physical activity study. Six could not walk, 3 were too young to walk, and 9 had incomplete data. Table 1 includes demographic data, body structure and function, mobility and functional activity status, and physical activity status. Children had a mean total steps of 3 847.63 (SD, 2029.62) per day and they were inactive 80.85% (SD, 9.15%) of the time or 19.2/24 hours in a day. Children spent 33.19% (SD, 13.11%) of their time in low activity, 51.5% (SD, 9.8%) in medium activity, and 16.01% (SD, 10.27%) in high activity.

TABLE 1 - Demographic, Body Structure and Function, Mobility and Functional Activity, and Physical Activity Measures

Variable	Mean (SD)	Range
Demographic
Age, y	7.76 (3.02)	3.25-13.22
Gender: female/male	12/13	–
Body structure and function
Body mass index	17.39 (3.31)	12.70-30.20
CTG repeat length	1 145.22 (327.29)	465.00-1800.00
Total lean mass, g	17 128.84 (7 678.02)	8 274.90-40 803.90
Mobility and functional activity measures
Walking 10 m, m/s	0.97 (0.26)	0.52-1.36
Rise from floor time, s	9.84 (11.31)	2.38-51.00
6-min walk distance, m	325.23 (109.85)	150.00-604.00
Physical activity measures
Mean total steps per day	3 847.63 (2 029.62)	288.40-6 930.80
Time inactive, %	80.85 (9.15)	66.80-97.60
Low steps, %	33.19 (13.11)	19.90-77.00
Medium steps, %	51.15 (9.80)	21.30-75.20
High steps, %	16.01 (10.27)	0-34.60

Abbreviations: CTG, cytosine-thymine-guanine; SD, standard deviation.

Total steps per day were significantly correlated with CTG repeat length (r = −0.60, P < .01, large effect size), suggesting that children with higher CTG repeat length took fewer total steps per day (Table 2). Percent time spent inactive was significantly correlated with CTG repeat length (r = 0.52, P = .01, large effect size), suggesting that children with higher CTG repeat length spent more time in inactivity. Percent time spent in high activity was significantly correlated with age (r = −0.44, P = .03, medium effect size), BMI (r = −0.46, P = .02, medium effect size), and lean mass (r = −0.54, P < .01, large effect size), suggesting that with increasing age, increased BMI, and increased lean mass, individuals spent less time in high activity (Figure).

Fig.: The relationship between percent time in high activity (left column) and inactivity (right column) for each variable (patient characteristics and physical activity measures). Linear trendlines are added. The asterisk within the graphs denotes significant correlations.

TABLE 2 - Correlation and Significance Data of Outcomes and Physical Activity Measures

Variable	Age, y	Body Mass Index	CTG Repeat	Total Lean Body Mass	10-m Gait Speed, m/s	Rise From Floor, s	6MWT, m
Total steps/d
Pearson	−0.27	−0.14	−0.60	−0.15	0.08	−0.36	0.24
P value	.19	.51	<.01a	.49	.70	.11	.29
Time spent in high activity, %
Pearson	−0.44	−0.46	−0.39	−0.54	0.03	−0.37	0.11
P value	.03a	.02a	.07	<.01a	.88	.10	.63
Time inactive, %
Pearson	0.16	0.20	0.52	0.10	−0.18	0.23	−0.24
P value	.46	.33	.01a	.65	.41	.31	.29

Abbreviations: CTG, cytosine-thymine-guanine; 6MWT, 6-minute walk test.

^aSignificance (P < .05).

There was no significant correlation observed for total steps/day or percent time in high activity or percent time inactive when accounting for mobility and functional activity measures: 6MWT, 10SS, and rise from floor (Table 2).

DISCUSSION

Our results support that children with CDM spend the majority of their time inactive and bouts of activity that do occur are spent in low to medium activity. In addition, age, BMI, CTG repeat length, and lean muscle mass may be factors influencing activity levels.

Children between the ages of 6 and 19 years should get 12 000 steps a day (both limbs) and 60 minutes of moderate to vigorous activity to meet physical activity guidelines.¹⁹ Although children with CDM are not expected to reach this maximum number of steps per day, findings indicate that children with CDM are completing only 32% of the daily recommended steps. Steps per day reported in this study are less than results reported in other studies assessing children with neurological/neuromuscular disorders.^20,21 Children with Duchenne muscular dystrophy, ages 5 to 13 years, averaged 4456 (SD, 513) steps per day,²² and children with cerebral palsy, ages 4 to 10 years, accrued 5801 (SD, 2312) steps per day.²¹

The significant association between CTG repeat length and inactivity and high activity as well as increasing CTG repeat length and increasing disease severity suggests that, as severity of CDM increases, childhood inactivity also increases. This may be related to already present impairments during the neonatal period in that a child's musculature may develop from a state of greater weakness. This presence of muscle weakness in conjunction with cognitive impairment may limit activity levels in children with CDM.

Researchers studying BMI and steps per day in boys with Duchenne muscular dystrophy found that a negative correlation for BMI and steps per day increasing BMI led to fewer steps.²² This study observed a negative correlation of BMI and high-intensity activity levels and negative correlation of lean body mass and high-intensity activity levels. These results may suggest a nutritional component.²³ Children with CDM have difficulty with oral motor dysfunction resulting in eating dysfunction.²⁴ In addition, they have higher rates of irritable bowel symptoms that may contribute to poor nutrition.⁶ Thus, poor nutrition leads to a calorie restriction, which may limit activity intensity in children with CDM. Collectively, strength loss and body composition cannot sustain higher intensity activity levels; however, more research is warranted to further investigate the relationship.

A mother's activity level is highly and significantly correlated with her child's and adolescent's activity level.²⁵ In this study population, all of the mothers also have DM1. Thus, the mothers may also have reduced physical activity and the mother-offspring correlation and the parent modeling may be a contributing factor to the reduced activity levels.

The functional outcome measures reported in this study do not appear to be good estimators of physical activity or inactivity that occurs at home and the community. Therefore, activity observed in the clinic may not aid a clinician in determining activity levels at home or community. There may be benefit of functional assessments conducted within a child's home and a benefit to include assessment of daily activity trends, to aid in identifying areas, which can be addressed in improving physical activity levels in the home or community.

The low activity level seen in these children is concerning because of the well-documented long-term benefit to health with participation in physical activity.⁷ In adults with DM1, individuals may benefit from moderate-intensity exercise.²⁶ Future short- and long-term studies should seek to identify benefits of increased physical activity in these children. Clinicians should be aware of physical activity recommendations and counsel parents and children on physical activity.

Limitations to this study include the small sample size; therefore, results should be interpreted with caution. Future studies can use these data for power analyses as well as guide regression analyses. Additional factors may be influencing the decreased activities that were not accounted for in this study including cognitive and behavioral influences, the effect of developmental delay, and fatigue. In addition, geographical and seasonal factors may play a role in the number of steps achieved and should be accounted for in future studies. There are differences in how studies are capturing and reporting physical activity in the home and community. Therefore, interpretation between studies should be reviewed cautiously. Future studies should seek both to identify aspects that may be influencing activity level for children with CDM and to identify ways to increase activity levels.

CONCLUSIONS

Children with CDM spend the majority of their time in inactivity, and bouts of activity that do occur are spent in low activity. There was a significant and negative correlation between the total steps per day and the time in inactivity and CTG repeats, suggesting increasing inactivity with increasing severity of CDM. Children with CDM in this study received only one-third the recommended amount of steps per day and had fewer steps per day compared with children with other neuromuscular disorders. The number of steps per day or time spent in inactivity or high activity is not correlated with clinical assessment tools. Future research should investigate what additional factors may be contributing to the inactivity level, such as cognitive and behavioral issues.