Johnson, Barbara A. PT, MSPH; MacWilliams, Bruce A. PhD; Carey, John C. MD, MPH; Viskochil, David H. MD, PhD; D'Astous, Jacques L. MD; Stevenson, David A. MD
Shriners Hospitals for Children Salt Lake City, Salt Lake City, Utah (Ms Johnson and Drs MacWilliams, Viskochil, D'Astous, and Stevenson); Department of Orthopedics (Drs MacWilliams and D'Astous) and Department of Pediatrics, Division of Medical Genetics (Drs Carey, Viskochil, and Stevenson), University of Utah, Salt Lake City, Utah.
Correspondence: David A. Stevenson, MD, Department of Pediatrics, Division of Medical Genetics, University of Utah, 2C412 SOM, 50 N Medical Dr; Salt Lake City, UT 84132 (firstname.lastname@example.org).
Grant Support: This research was carried out with support from a research grant 1 K23 NS052500 from the National Institute of Neurological Disorders and Stroke, Doris Duke Charitable Foundation Clinical Scientist Development Award, Shriners Hospitals for Children Research Foundation, and the Children's Health Research Center and Clinical Genetics Research Program at the University of Utah.
This research fulfills part of the requirements for the degree of doctor of philosophy (disability studies) for Ms Johnson.
Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders presenting in childhood with an incidence of 1 per 3000. Examples of the clinical manifestations of NF1 include café-au-lait macules, tumors of peripheral nerves, optic pathway tumors, long-bone dysplasia, developmental delays, and learning disabilities. NF1 is associated with skeletal abnormalities such as short stature, scoliosis, and long-bone fracture with nonunion. Children with NF1 have abnormalities of bone and muscle as evidenced by decreased bone mineral density, decreased bone strength, and low muscle mass, all of which may predispose them to fractures and scoliosis.1,2 Adults with NF1 demonstrate decreased muscular force in hand grip strength.3
Children with NF1 have been reported to have specific learning disabilities, attention-deficit/hyperactivity disorder, delays in language, executive functioning, visual perceptual skills, and memory contributing to problems with academic achievement.4 They also have poorer performance in neuromotor functions than their siblings who are unaffected5–7 and they are at a 6-fold increased risk for receiving remedial teaching for learning, behavior, speech, or motor problems.8 Chapman et al6 examined 10 children with NF1, using a structured evaluation of behavioral observations, and found a consistent profile of motor disinhibition and awkward motor output.
The cognitive problems and the musculoskeletal impairments in children with NF1 may contribute to difficulty learning and executing motor skills. Whereas previous research investigations have described the cognitive, behavioral, and musculoskeletal impairments in children with NF1, there is a lack of research analyzing the motor proficiency of children with NF1 using reliable outcome measures designed to specifically evaluate the motor skills of children. The Bruininks-Osertsky Test of Motor Proficiency–second edition (BOT 2) has been found to be a reliable measure of motor proficiency and is one of the most frequently used assessments for evaluating and discriminating motor proficiency in children.9 The BOT 2 was found to be a reliable outcome measure for evaluating motor proficiency in children with intellectual disorders.10 The current study reports the motor proficiency outcomes in children with NF1 and documents the ability of the BOT 2 to characterize motor proficiency in NF1.
Previously published effect sizes10 and population variances reported in the BOT 2 manual11 were used to calculate power and resulted in an estimate of N = 26 (G*power 3, Heinrich-Heine University, Dusseldorf, Germany). Children with NF1 were recruited from the University of Utah NF1 Clinic and through advertising with a local NF1 support group organized by the Children's Tumor Foundation. Subjects were examined by 1 investigator (D.S.) to confirm the clinical diagnosis of NF1. Only individuals who fulfilled the NIH clinical diagnostic criteria for NF1 were included.12,13 Exclusion criteria were the presence of a visual impairment, an orthopedic procedure within the last 6 months, and tibial dysplasia. These conditions were excluded to reduce the influence of visual impairments on eye-hand coordination and the influence of surgery or musculoskeletal impairments on motor skill performance. Children younger than 4 years were not included because of limitations of the BOT 2 instrument in young children. Institutional review board approval for the study was obtained from the University of Utah. All children who agreed to participate and met the inclusion criteria were enrolled in the study and completed the evaluation.
Participants were assessed at the Shriners Hospitals for Children Salt Lake City Movement Analysis Lab by an experienced physical therapist (B.J.). Their height and weight were measured and the percent BMI was calculated.14 Their motor proficiency was examined using the BOT 2.11 This test instrument is an individually administered measure of fine and gross motor skills of children aged 4 through 21 years. The test consists of 8 subtests, which measure fine motor precision, fine motor integration, manual dexterity, upper limb coordination, bilateral coordination, balance, running speed/agility, and strength. The subtest scores are combined into 4 motor area composite scores. Each motor-area composite consists of 2 subtests that assess related aspects of motor function. The 4 motor area composites are as follows: (1) fine manual control (control of the distal musculature of the hands in performing fine motor skills), (2) manual coordination (control and coordination of the arms and hands), (3) body coordination (control and coordination of posture and balance), and (4) strength and agility (aspects of fitness and performance of gross motor skills). A “Total Motor Composite” score is generated from the above 4 motor area composite scores representing an overall score for motor proficiency. Composite scores are categorized into 5 groups: well-above average (Z score of 2 or greater), above average (Z score of 1−2), average (Z score of 1 to −1), below average (Z score of −1 to −2), and well-below average (Z score of −2 or less).
The normative sample of the BOT 2 included 1520 youth stratified by age and gender and included children with developmental disabilities. Interrater reliability, test-retest reliability, and internal consistency were moderate to strong (>0.80).11 Content validity, internal structure, and relationships with other measures of motor performance were strong (r = 0.80).
Data were analyzed using SPSS v. 17.0 (Chicago, Illinois). The distributions of Z scores for each composite score were evaluated using Q-Q plots and were found to be normally distributed. Differences between Z scores for the males and females and the 3 age groups were evaluated with an independent t test and 1-way ANOVA. The mean Z scores were calculated for each composite using the tables in the BOT 2 manual, and then a Z table was used to identify a critical value (P < .05). The relationship of composite scores to the total motor composite score was evaluated using simple linear regression. The age- and sex-specific mean scores for each subtest were used for comparison since previous literature found differences between males and females in some age categories.15 One sample t tests were used to compare the NF1 group subtest mean scores with BOT 2 subtest mean scores.
Twenty-six children (aged 4-15 years) with NF1 were assessed using the BOT 2 (Table 1). There were 13 males and 13 females. The mean age was 8.25 years (SD = 3.25). Fifty-four percent of the children were in the 4- to 7-year age range. There were no statistically significant differences between males or females (P = .26) or between the scores of the children in the 3 age ranges (P = .17). Children in the NF1 group had a mean percent body mass index of 38% (SD = 30).
The age- and sex-specific scores were used to determine raw scores for each subtest using the BOT 2 manual. The raw scores were converted to composite scores and Z scores by using the test manual. The NF1 group of children had statistically significant lower scores (Z = −1.62, P < .05) than the normative test sample for the Total Motor Composite (Table 2). No individual had a “Total Motor Composite” score in the above-average or well-above-average range. Nineteen percent (N = 5) of the NF1 group scored in the average category, 54% (N = 14) scored in the below-average category, and 27% (N = 7) scored in the well-below-average category. The mean Z scores for males (−1.77) were lower than the mean Z scores for females (−1.33), although this difference was not statistically significant. The strength and agility mean composite Z score was the lowest (−1.48) followed by body coordination mean composite Z score (−1.37) (Table 3). Regression analysis of the relationship between the motor area composite scores and total motor composite score revealed that 67% of the variance was accounted for by the strength and agility composite score. Sixty-one percent of the variance was accounted for by the fine manual composite score (Table 4).
The results of the 1-sample t test resulted in significantly lower scores for fine motor precision, fine manual integration, upper limb coordination, bilateral coordination, balance, run speed/agility, and strength. Manual dexterity scores were not significantly different (Table 5). Cohen's d was calculated to determine effect size using the mean standard deviation scores reported in the BOT 2 manual. There was a small effect size for manual dexterity (d = 0.23), a moderate effect size for fine motor integration (d = 0.69), and a large effect size for fine motor precision (d = 1.24), upper limb coordination (d = 1.33), bilateral coordination (d = 1.21), balance (d = 1.69), run speed/agility (d = 1.28), and strength (d = 1.16).16
The NF1 group demonstrated statistically significant lower motor proficiency compared to the BOT 2 normative data. The BOT 2 was useful in characterizing the NF1 group's motor proficiency. The strength and agility composite score explained a large portion of the variance in the total motor composite score. Running speed and strength subtests are combined to calculate the strength and agility motor area composite score. Both of these subtest scores were significantly lower than age- and sex-matched normative subtest scores. Wrotniak et al17 found that a positive relationship exists between motor proficiency and physical activity level in children, and the observed motor proficiency impairments associated with NF1 may make it difficult for children with NF1 to engage in recreation and leisure activities. Because children with NF1 are reported to have decreased bone mineral density1 and increased fracture rates,2 possibly decreased physical activity and the lack of load-bearing activities contribute to osteopenia and fractures. Given that jumping activities during adolescent growth increase bone mass,18,19 improving motor proficiency to increase jumping may result in improved bone mass accrual. Motor training programs have improved motor skills20 and motor function21 in children with developmental coordination disorder, and similar motor training programs may be an effective intervention to improve motor proficiency in children with NF1. We are not aware of any studies evaluating the efficacy of therapeutic exercise in children with NF1, although physical therapy interventions may be appropriate to improve motor proficiency. Targeting strength, agility, bilateral coordination, and balance within a training program seems reasonable based on the deficits reported herein.
The body coordination score (combination of balance and bilateral coordination subtests) contributed 35% of the variance in the total motor composite score. Wuang and Su10 reported low sensitivity (32.65%) and high specificity (84.31%) for the balance section of the BOT 2. The BOT 2 may be better at identifying children who do not have balance impairments than identifying those with balance impairments. It will be necessary to use a more sensitive measure for detecting balance impairments, such as center-of-pressure measures on a force plate. Balance may play a role in contributing to low motor proficiency in children with NF1 since the mean balance score differences and the effect sizes were large. However, additional testing is recommended to evaluate balance ability. Balance and coordination impairments may play a role in increased fracture rates in individuals with NF1 and future research is necessary to rule out the possibility of clumsiness and falls contributing to the increased fracture rate.
The NF1 group also had significantly lower scores on the BOT 2 in fine motor skills. The fine manual control composite score accounted for 61% of the variance of the total motor composite score. Fine motor precision, fine motor integration, and upper limb coordination subtest scores were significantly lower than the BOT 2 normative data. Because fine motor skills such as writing, drawing, cutting, and keyboarding are important for academic work, fine motor limitations should also be explored to determine whether they contribute to the academic difficulties seen in children with NF1. Hyman et al7 studied 81 children with NF1 and 49 of their siblings. Problems with academic achievement were present in 52% of children with NF1 as compared with 8% of their siblings. Specific learning disabilities were identified in 20% of the children and the remaining 32% had general learning problems. We found similar numbers of children with motor proficiency impairments. Fifty-four percent of the NF1 groups' total motor composite scores fell in the below-average category, and 27% fell in the well-below-average category. It is our clinical experience that parents of children with NF1 report concerns about their children's motor abilities. However, these motor deficiencies may be subtle and not be recognized without a detailed assessment of their motor functions. We propose that all children with NF1 should be screened for motor delays and referred for occupational and physical therapy services if delays are identified.
The current study investigated a relatively small number of children from one regional center. In addition, the parents who enrolled their children in the study may have been more concerned about their children's coordination leading to a potential bias in our sample. Therefore, further investigation with additional individuals with NF1 from multiple sites will be important. Another limitation is that even though children with NF1 show statistically significant lower motor proficiency, this change may not be clinically important. We found large effect sizes for 6 of the 8 subtests and these effect sizes reflect differences in motor proficiency of 1.16 to 1.69 SDs between the NF1 group and the BOT 2 mean scores. In particular, 27% of the NF1 group's total motor composite scores fell in the well-below-average category (>2 SDs below the mean), qualifying them for special education services in most educational settings.
The BOT 2 was useful in identifying and characterizing fine and gross motor delays in children with NF1. The NF1 group had decreased total motor proficiency and showed the greatest difference in their balance and strength subtest scores, followed by running speed and agility, fine motor precision, upper limb coordination, bilateral coordination, and fine motor integration. These results are likely to be clinically important because lower motor proficiency may limit children with NF1 from performing the running and jumping activities necessary for improving bone strength and mass. The results are also likely to be relevant to academic performance since fine motor skills are important for writing, keyboarding, and cutting activities at school. Given that 81% of the children with NF1 had below-average or well-below-average scores for total motor proficiency, physical therapy would likely be beneficial for a large subset of children with NF1. Deficiencies were seen in 7 of the 8 subtests (fine motor precision, fine motor integration, upper limb coordination, bilateral coordination, balance, run speed/agility, and strength) suggesting that an approach focusing on multiple aspects of motor proficiency will be needed when designing physical therapy interventions. Particular attention should be given to strength and agility as this motor composite category contributed largely to the overall motor proficiency deficit.
Further research is indicated to establish a relationship between poor motor proficiency, physical inactivity, and the musculoskeletal impairments seen in children with NF1. Future clinical trials utilizing interventions to improve motor proficiency in children with NF1, both pharmacologic and nonpharmacologic, will require the use of validated endpoints. The BOT 2 instrument is a potential tool, which could be used in future clinical trials for measuring motor proficiency in NF1.
We thank Jeanne Siebert, Susan Geyer, Janice Davis, Meredith Winn, Heather Hanson, and Stephanie Bauer for coordination. We thank Amy Shuckra, PT, DPT, and Soffe Lowell for help with data collection. We also thank Judith Holt, PhD, for her advice; Scott DeBerard, PhD, for advice on statistical analysis; and Dr James Roach, Dr Elizabeth Schorry, Dr Alvin Crawford, Dr Linlea Armstrong, Dr J. Friedman, and Patricia Birch for their help, discussion, and insight. We thank the participants and their families.
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age factors; child; motor performance; motor skills; neurofibromatosis type 1; sex factors
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