Tim Niiler

Growth in individuals with Majewski osteodysplastic primordial dwarfism type II caused by pericentrin mutations

Microcephalic primordial dwarfism (MPD) is a class of disorders characterized by intrauterine growth restriction (IUGR), impaired postnatal growth and microcephaly. Majewski osteodysplastic primordial dwarfism type II (MOPD II) is one of the more common conditions within this group. MOPD II is caused by truncating mutations in pericentrin (PCNT) and is inherited in an autosomal recessive manner. Detailed growth curves for length, weight, and OFC are presented here and derived from retrospective data from 26 individuals with MOPD II confirmed by molecular or functional studies. Severe pre‐ and postnatal growth failure is evident in MOPD II patients. The length, weight, and OFC at term (when corrected for gestational age) were −7.0, −3.9, and −4.6 standard deviation (SD) below the population mean and equivalent to the 50th centile of a 28–29‐, 31–32‐, and 30–31‐week neonate, respectively. While at skeletal maturity, the height, weight, and OFC were −10.3, −14.3, and −8.5 SD below the population mean and equivalent to the size of 3‐year 10‐ to 11‐month‐old, a 5‐year 2‐ to 3‐month‐old, and 5‐ to 6‐month‐old, respectively. During childhood, MOPD II patients grow with slowed, but fairly constant growth velocities and show no evidence of any pubertal growth spurt. Treatment with human growth hormone (n = 11) did not lead to any significant improvement in final stature. The growth charts presented here will be of assistance with diagnosis and management of MOPD II, and should have particular utility in nutritional management of MOPD II during infancy.

Persistence and Recurrence Following Femoral Derotational Osteotomy in Ambulatory Children With Cerebral Palsy

Background: Excessive hip internal rotation is frequently seen in children with cerebral palsy (CP). Femoral derotational osteotomy (FDO) is effective in the short term, but factors associated with long-term correction remain unclear. The purposes of this study were to define the incidence of persistence and recurrence of hip internal rotation following FDO in ambulatory children with CP and to evaluate factors that influence outcome. Methods: Following IRB approval, kinematic and passive range of motion (PROM) variables were retrospectively evaluated in children with spastic CP who had FDO to correct hip internal rotation as part of clinical care at a children’s specialty hospital. Children included had a preoperative evaluation (Vpre), a short-term postoperative evaluation (Vshort, 1 to 3 y post), and, in some cases, a long-term postoperative evaluation (Vlong, ≥5 y post). Age at surgery, physical exam measures, and kinematics variables were evaluated as predictors for dynamic and static recurrence. Results: Kinematic hip rotation improved from 14±12 degrees (Vpre; internal positive) to 4±13 degrees (Vshort) and relapsed to 9±15 degrees long term (P<0.05 Vpre/Vshort/Vlong; 99 limbs). Hip PROM midpoint improved from 23±9 degrees (Vpre) to 8±11 degrees (Vshort) and relapsed to 14±13 degrees (P<0.01 Vpre/Vshort/Vlong). Persistent hip internal rotation was noted in 41% (kinematics) and 18% (PROM) of limbs at Vshort (105 children, 178 limbs). Of limbs that showed initial improvement at Vshort (62 children, 95 limbs), recurrence was seen in 40% (kinematic hip rotation) and 39% (hip midpoint) at Vlong. Comparing children who had recurrent hip internal rotation and those who maintained long-term correction, we saw higher levels of spasticity and lower gait velocity in the recurrent group (P<0.05). Conclusions: Although FDO is an accepted treatment in children with CP, persistence and recurrence of hip internal rotation can occur. Recurrence is associated with spasticity and slower gait velocity. Predictor variables may be useful for surgeons during preoperative discussions of expected outcome with families of FDO candidates. Level of Evidence: Level III.

Factors Related to Increased Ulnar Collateral Ligament Thickness on Stress Sonography of the Elbow in Asymptomatic Youth and Adolescent Baseball Pitchers

Background: Stress ultrasound (SUS) of the elbow has demonstrated changes in the anterior band of the ulnar collateral ligament (UCL) in professional and high school–aged pitchers. However, there have been no large reports correlating pitching history data with SUS changes in youth and adolescent baseball pitchers. Hypothesis: Changes of the UCL on SUS will correlate with pitching volume in youth and adolescent baseball pitchers. Study Design: Cross-sectional study; Level of evidence, 3. Methods: SUS of the elbow was performed in both elbows of 102 youth and adolescent baseball pitchers. UCL thickness and the width of the ulnohumeral joint, at rest and with 150 N of valgus stress, were measured using a standardized, instrumented device. Demographic data, arm measurements, and a pitching history questionnaire were recorded as well. The pitchers were separated into 2 groups based on age: group 1 (12-14 years) and group 2 (15-18 years). SUS findings of the dominant elbows were compared between the 2 groups. Correlation analysis and linear regression were used to identify relationships between SUS findings and pitching history data. Results: In all pitchers, the mean UCL thickness was 4.40 mm in the dominant elbow and 4.11 mm in the nondominant elbow (P =.03). There was no significant difference between elbows in any joint space characteristics. A comparison of group 1 versus group 2 demonstrated significant differences in UCL thickness (4.13 vs 4.96 mm; P < .001), resting joint space width (6.56 vs 4.04 mm; P < .001), and stressed joint space width (7.68 vs 4.07 mm; P < .001). There was no difference in the change in joint space width between the 2 groups (1.11 vs 0.76 mm; P = .05). The UCL was significantly thicker in pitchers who threw more than 67 pitches per appearance (4.69 vs 4.14 mm), who pitched more than 5 innings per appearance (4.76 vs 4.11 mm), and who had more than 5.5 years of pitching experience (4.71 vs 4.07 mm; P < .001). Linear regression demonstrated that age, weight, and pitches per appearance (R 2 = 0.114, 0.370, and 0.326, respectively) significantly correlated with UCL thickness. Conclusion: These findings suggest that UCL thickness increases as pitchers get older and heavier and as they increase their pitch volumes.

The effectiveness of posterior knee capsulotomies and knee extension osteotomies in crouched gait in children with cerebral palsy.

Crouched gait is common in children with cerebral palsy (CP), and there are various treatment options. This study evaluated the effectiveness of single-event multilevel surgery including posterior knee capsulotomy or distal femoral extension osteotomy to correct knee flexion contracture in children with CP. Gait analyses were carried out to evaluate gait preoperatively and postoperatively. Significant improvements were found in physical examination and kinematic measures, which showed that children with CP and crouched gait who develop knee flexion contractures can be treated effectively using single-event multilevel surgery including a posterior knee capsulotomy or distal femoral extension osteotomy.

Growth charts for individuals with rhizomelic chondrodysplasia punctata

Rhizomelic chondrodysplasia punctata (RCDP) is a class of peroxisomal disorders characterized by defective plasmalogen biosynthesis. There are multiple recognized types of RCDP, all of which have autosomal recessive inheritance, and their associated genes are known: RCDP type 1 with PEX7, RCDP type 2 with GNPAT, RCDP type 3 with AGPS, RCDP type 4 with FAR1, and RCDP type 5 with PEX5. Among other medical/developmental issues, plasmalogen deficiency has a direct effect on bone growth and results in postnatal growth failure, the severity of which corresponds to the degree of plasmalogen deficiency. In order to document growth in patients with RCDP, we present detailed growth curves for length, weight, and head circumference derived from retrospective data from 23 individuals with RCDP types 1 and 2 confirmed by molecular and/or biochemical studies. We stratified growth curves by age as well as by plasmalogen level, with those with higher plasmalogens grouped as “non‐classic.” The growth charts presented here provide guidance to families and physician caretakers on the natural course of growth in individuals with RCDP during infancy into early childhood, and thus will have particular utility in setting expectations and guiding optimal feeding interventions in this population.© 2016 Wiley Periodicals, Inc.

Reliability and minimal detectable change in foot pressure measurements in typically developing children

BACKGROUND In pedobarography, clinically meaningful comparison of measurements within or between subjects is limited by data variability and measurement error. This study aims to determine the components of the minimal detectable change (MDC) in impulse across all foot regions and the reliability of these measures. METHODS A convenience sample of foot pressures from 108 visits by normal, healthy subjects aged 2-17 years was studied. Each subject had three pedobarograph measurements taken per foot, with six subjects returning for a second visit for assessment of day-to-day variability. Using a five-region mask, segmental impulses were determined, and from these we obtained the coronal plane pressure index (CPPI). Inter-rater, intra-rater, and day-to-day data were analyzed using intraclass correlation coefficients (ICC) to quantify reliability. Variability of the data was analyzed to quantify the MDC. RESULTS Inter- and intra-rater reliability was high for all measurements while variability was low, indicating small direct measurement error. Generally, the largest contributing factor to the MDC was day-to-day variability. Step-to-step variability was more dependent on foot segment than age although minor age-related changes were noted. Finally, the high relative variability in the CPPI and the medial mid foot impulse resulted in very high MDCs for these measures.

Flexed-knee gait in children with cerebral palsy

Aims The purpose of this study was to evaluate the long‐term outcome of adolescents with cerebral palsy who have undergone single‐event multilevel surgery for a flexed‐knee gait, followed into young adulthood using 3D motion analysis. Patients and Methods A total of 59 young adults with spastic cerebral palsy, with a mean age of 26 years (SD 3), were enrolled into the study in which their gait was compared with an evaluation that had taken place a mean of 12 years (SD 2) previously. At their visits during adolescence, the children walked with excessive flexion of the knee at initial contact and surgical or therapeutic interventions were not controlled between visits. Results Based on the change in flexed‐knee gait over approximately ten years, improvements were seen in increased Gait Deviation Index (p < 0.001) and decreased flexion of the knee at initial contact (p < 0.001). Greater popliteal angle (p < 0.001), reduced Gross Motor Function Measure section D (p = 0.006), and reduced speed of gait (p = 0.007) suggested a mild decline in function. Quality‐of‐life measures showed that these patients fell within normal limits compared with typical young adults in areas other than physical function. Conclusion While some small significant changes were noted, little clinically significant change was seen in function and gait, with gross motor function maintained between adolescence and young adulthood.

Comparison of three-dimensional multi-segmental foot models used in clinical gait laboratories

BACKGROUND Many skin-mounted three-dimensional multi-segmented foot models are currently in use for gait analysis. Evidence regarding the repeatability of models, including between trial and between assessors, is mixed, and there are no between model comparisons of kinematic results. RESEARCH QUESTION This study explores differences in kinematics and repeatability between five three-dimensional multi-segmented foot models. The five models include duPont, Heidelberg, Oxford Child, Leardini, and Utah. METHODS Hind foot, forefoot, and hallux angles were calculated with each model for ten individuals. Two physical therapists applied markers three times to each individual to assess within and between therapist variability. Standard deviations were used to evaluate marker placement variability. Locally weighted regression smoothing with alpha-adjusted serial T tests analysis was used to assess kinematic similarities. RESULTS All five models had similar variability, however, the Leardini model showed high standard deviations in plantarflexion/dorsiflexion angles. P-value curves for the gait cycle were used to assess kinematic similarities. The duPont and Oxford models had the most similar kinematics. CONCLUSIONS All models demonstrated similar marker placement variability. Lower variability was noted in the sagittal and coronal planes compared to rotation in the transverse plane, suggesting a higher minimal detectable change when clinically considering rotation and a need for additional research. Between the five models, the duPont and Oxford shared the most kinematic similarities. While patterns of movement were very similar between all models, offsets were often present and need to be considered when evaluating published data.

Expected weight gain for children with microcephalic osteodysplastic primordial dwarfism type II

To the Editor: Microcephalic osteodysplastic primordial dwarfism type II (MOPDII; OMIM #210720), first described by Majewski, Ranke, and Schinzel (1982), is the most common distinctive diagnostic entity within the group of microcephalic primordial dwarfism syndromes (Hall, Flora, Scott, Pauli, & Tanaka, 2004; Klingseisen & Jackson, 2011; Rauch, 2011). Aside from the classic features of severe preand post-natal growth failure together with microcephaly, individuals with MOPDII have a characteristic skeletal dysplasia (Hall et al., 2004; Willems et al., 2009) with a specific hip pathology (Karatas et al., 2014), abnormal dentition (Kantaputra et al., 2011), an increased risk for cerebrovascular disease (Bober et al., 2010; Brancati, Castori, Mingarelli, & Dallapiccola, 2005; Waldron et al., 2009), and insulin resistance (Huang-Doran et al., 2011). MOPDII has autosomal recessive inheritance and is caused by mutations in the pericentrin (PCNT) gene (Rauch et al., 2008). Typically, infants born small for gestational age are fed aggressively in an attempt to improve growth (Hall et al., 2004). However, given the underlying nature of MOPDII, typical growth velocities are unattainable. It is our experience that many individuals with MOPDII have gastrostomy tubes recommended, if not placed, in the neonatal period, given their exceedingly slow weight gain. In order to help guide management of the child with MOPDII, we previously published detailed growth curves for height, weight, and head circumference, as well as weight for height curves to assess proportions, for 26 individuals with MOPDII with PCNT mutations or demonstrated absence of PCNT protein (Bober et al., 2012). It has since become apparent that a valuable metric to help guide the nutritional management of an infant with MOPDII is having an appropriate expectation of weight gain per day by age. We recently generated this type of curve for a different dysplasia diagnosis, and it has proven quite helpful in the clinical setting (Duker et al., 2017). To that end, we are including here the grams per day expectations from birth to 17 years for individuals with MOPDII, using the same ascertainment of patients published in Bober et al. (2012). To date, 32 patients in the Nemours IRB approved Primordial Dwarfism Registry have molecular confirmation of their MOPDII diagnosis as well as weight measurements for analysis. Longitudinal weight data comprising 446 distinct datum from 32 patients (15 female, 17male) ranging in age frombirth to 28 yearswere analyzed. Data point count binned by year is noted in Supplemental Figure S1. All data utilized were from prior to the initiation of any growth hormone supplementation. Weight versus age data were resampled with replacement 100 times and fit using a locally weighted regression model (LOESS) with a span of 0.99 (Cleveland, Grosse, & Shyu, 1992). The derivative of this fit was calculated using a central difference method, and then re-smoothed using LOESS with a span of 0.90. Span parameters which dictated the degree of smoothing in the model were chosen to ensure monotonic increases or decreases in the data and smooth out local effects that might imply non-existent decreases in weight as age increased. The resultant weight-velocity curve was the mean of the bootstrapped curves surrounded by a band indicating the bootstrapped standard deviation. This was then plotted both from birth to 17 years. Because later data was from a single subject whose mean weight was below the group average, this caused an unrealistic down-turn in the weight versus age graph. All statistics were done using R statistical software (R Core Team, 2017). As noted in Figure 1, and contrasting with a typical neonate, infants with MOPDII have an expected weight gain of approximately 2 g/d throughout their first year of life. As the figure continues to