Raoul H. H. Engelbert

The aim of this study was to investigate the relationship between the presence and localization of joint hypermobility and delay in motor development. A retrospective chart review was performed. All children younger than 2.5 years of age and between four and 12 years of age with generalized joint hypermobility were included. Generalized joint hypermobility was assessed using the criteria of Bulbena. In children between one and 2.5 years of age, motor development was measured using the Bayley Scales of Infant Development. In children four to 12 years of age, the Movement Assessment Battery for Children was used. Data from 72 children were available for analysis. In nine of 16 children younger than 2.5 years of age, a delay in motor development was found without a significant association between the delay in motor development (yes/no) and the Bulbena score (odds ratio: 0.4; 95% confidence interval: 0.07–2.1). In children between four and 12 years of age, a severe delay in motor development was present in 14 of 56 children (25%), while 12 of 56 children (21%) were at risk and 30 of 56 (54%) were age appropriate. No significant association between delay in motor development and the Bulbena score was found (odds ratio: 1.3; 95% confidence interval: 0.8–2.1). The age of independent walking was not significantly associated with the number of hypermobile joints (Bulbena score) (linear regression coefficient: 0.3; 95% confidence interval: −1.5 – 2.1). Although severe delays in motor development may be observed in approximately one third of children with generalized joint hypermobility, there is no association between the amount of generalized joint hypermobility and delay in motor development.

Objective. To describe the clinical features, osseal characteristics, and collagen biochemistry in children who attended our clinic with predominantly generalized hypomobility of the joints, in combination with musculoskeletal complaints or abnormal walking, and no known syndrome or known rheumatic, neurologic, skeletal, metabolic, or connective tissue disorder was present. Methods. Nineteen children who attended the Children’s Hospital of the University Medical Center Utrecht for generalized hypomobility of the joints (mean age: 11.6; standard deviation: 2.7), in combination with musculoskeletal complaints or abnormal walking as primary complaints (symptomatic generalized hypomobility [SGH]), were compared with an age-matched reference group of 284 healthy children with normal mobility of the joints. Anthropometrics, range of joint motion, muscle strength, exercise tolerance, motor development, quantitative ultrasound measurements of bone, and degradation products of collagen in urine were studied. Collagen modifications were determined in skin biopsies of 3 children and in hypertrophic scar tissue of another child, all with SGH. Results. The range of joint motion was significantly decreased in almost all joints of all 19 children and after adjustment for age, gender, body weight, and height, significantly lower than that of the reference group (−108.3 degrees; 95% confidence interval [CI]: −136.9 to −79.8). Quantitative ultrasound measurements as well as urinary pyridinoline cross-link levels were, after adjustment for possible confounders, significantly lower in SGH children (broad-band ultrasound attenuation: −9.6 dB/MHz [95% CI: −17.4 to −1.9]; speed of sound: −25.0 m/s [95% CI: −39.7 to −10.3]; hydroxylysylpyridinoline: −50.1 μmol/mmol [95% CI: −87.6 to −12.6], lysylpyridinoline: −21.3 μmol/mmol [95% CI: −34.0 to −8.6]). An increased amount of pyridinoline cross-links per collagen molecule was observed in skin and hypertrophic scar tissue, in combination with increased amounts of collagen. Conclusion. SGH in children is considered a new clinical entity with specific clinical characteristics and might be related to an increased stiffness of connective tissue as a result of higher amounts of collagen with increased cross-linking.

We studied the effects of spondylodesis on spinal curvature, functional outcome, level of ambulation and perceived competence in 11 children with osteogenesis imperfecta (OI). Mean age at surgical intervention was 13.1 years (SD 2.5 years) and follow-up amounted to 3.4 years (SD 2.3 years). Spinal curvature was measured according to Cobb. The level of ambulation was scored according to the modified criteria of Bleck. Functional abilities and the amount of parental assistance were scored using the Dutch version of the Pediatric Evaluation of Disability Inventory (PEDI). Perceived competence was measured using the Harter Self-Perception Profile for Children. The amount of fatigue, spinal pain and presence of subjective dyspnea were scored with a visual analog scale. The median progression per year before spondylodesis was 6.1° (interquartile range 2.9°–12.9°) and after the spondylodesis it was 5.0° (interquartile range 1.6°–11.0°). No significant progression or regression in the level of ambulation was found. Perceived competence improved slightly. In the total score of the perceived competence, a borderline significant increase was found (P-value 0.068). We concluded that spinal fusion in children with OI does not materially influence functional ability and level of ambulation. Self-perceived competence seemed to improve after surgery. The amount of pain, fatigue and subjective dyspnea seemed to diminish after spinal surgery. Progression of scoliosis proceeded, as did development of spinal curvature at the junction of the spondylodesis. Therefore, oral or intravenous bisphosphonates before and after spinal surgery should be considered.

Asymmetry in infancy is a diagnosis with a large spectrum of features, expressing an abnormal shape of parts of the body or unequal postures and movements. Symptoms may be structural and/or functional, with localised or generalised expression. Within the last decade, many professionals have focused on the adverse consequences on motor performance of infants, associated with the recommendations on the prevention of sudden infant death. The purpose of the present study was to highlight different aspects of asymmetry in infancy based on best available evidence in the current literature and to present a flow chart illustrating different diagnostic pathways of asymmetry in infancy. Conclusion:we conclude that asymmetry in infancy is a diagnosis with a large spectrum of features and a multifactorial aetiology without consensus in definition, nomenclature and classification. Systematic diagnostic management of asymmetry in infancy is indicated. The presented diagnostic flow chart might serve as a basis.

We studied the relationship between the age of reaching motor milestones, especially anti-gravity activities, and the age of development of pathological spinal curvatures in children with osteogenesis imperfecta (OI). We hypothesized that earlier achievement of anti-gravity motor milestones predicts a later development of pathological spinal curvatures. Ninety-six children participated in this retrospective study. The severity of the disease was classified according to Sillence into types I–IV. Spinal radiography was performed annually and spinal deformities were measured according to the Cobb angle. Scoliosis was defined as a Cobb angle exceeding 9°. Pathological thoracic kyphosis was defined as a Cobb angle exceeding 40°. The parents were asked to report the age at which the child achieved motor milestones, and data were checked against health care records. Thirty-seven of 96 children (39%) developed a scoliosis of more than 9°. Nine of 96 children (9%) developed a pathological kyphosis. The age of developing scoliosis was significantly lower than the age of development of the pathological kyphosis (P=0.01). Bone mineral density was measured by dual energy X-ray absorptiometry (DEXA) in 53 children, 28 of whom developed scoliosis, and 25 of whom did not. The mean DEXA Z-score of the 28 children with scoliosis was significantly lower than that of the 25 children without (–5.2, SD 1.3 vs –3.2, SD 1.9; P-value <0.001). Children with OI type IV, but particularly OI type III, reached motor milestones much later than children with OI type I. The motor milestone "supported sitting" showed a significant inverse association with time of the first presence of scoliosis with a Cobb angle greater than 9° (linear regression coefficient: –1.3, 95% confidence interval: –2.6 to –0.03). The age of achieving the motor milestones "lifting the head to 45° in prone position", "rolling", and "supported-" and "unsupported standing" were not significantly associated with age of the first presence of scoliosis with a Cobb angle greater than 9°. However, the directions of associations suggest that here, too, there is a tendency for later development of scoliosis in those who reach milestones at earlier ages. Multivariable analyses showed that the motor milestone "sitting with support" was significantly associated with age of first achieving scoliosis, independent of gender and type of OI (linear regression coefficient: –0.9, 95% confidence interval: –1.3 to –0.5). We conclude that in children with OI, the age of anti-gravity motor milestones was associated with the age of development of pathological spinal curvatures. Earlier achievement of the motor milestone "supported sitting" predicted significantly a later development of pathological spinal curvatures, independent of gender and type of OI.

Objectives. Children with generalized hypermobility of the joints and musculoskeletal complaints frequently visit pediatric clinics, but many show no currently known collagen or other possibly related diseases. Whether the symptoms are confined to the musculoskeletal system is unknown. We assessed whether such children have detectable differences in laxity of connective tissue present in organ systems other than joints. We also assessed whether children with generalized joint hypermobility and musculoskeletal complaints have more profound systemic changes in connective tissue of various organ systems as compared with children with generalized joint hypermobility without musculoskeletal complaints. Methods. Anthropometrics, range of joint motion, muscle strength, skin extensibility, blood pressure, quantitative ultrasound measurements of bone, and degradation products of collagen were studied in 15 prepubertal children with generalized joint hypermobility and musculoskeletal complaints and compared with a population-based reference group of 95 nonsymptomatic prepubertal children. Symptomatic hypermobile children were also compared with children of the population-based reference group who had asymptomatic hypermobility of the joints (n = 16). Results. Children with symptomatic generalized joint hypermobility had significantly higher skin extensibility (5.6 mm/15 kPa, 95% confidence interval [CI]: 4.0–7.1), lower quantitative ultrasound measurements (speed of sound: −26.8 m/s; 95% CI: −41.1 to −12.6) in bone, and lower systolic and diastolic blood pressure (−8.0 mmHg, 95% CI: −13.3 to −2.8; and −6.0 mmHg, 95% CI: −10.0 to −2.2, respectively) as compared with the total reference group. Also, they had significantly lower excretion of urinary hydroxylysylpyridinoline cross-links (mean difference: −51.3 μmol/mmol; 95% CI: −92.2 to −10.4) as well as lysylpyridinoline cross-links (−18.7 μmol/mmol; 95% CI: −36.9 to −0.5). Age, gender, body weight, height, and particularly cross-links excretion did not explain group differences in clinical and bone characteristics. After adjustment for age, gender, body weight, and height, children with symptomatic generalized joint hypermobility (n = 15) had significantly higher total range of joint motion (117.8 degrees; 95% CI: 77.7–158.0), skin extensibility (3.5 mm/15 kPa; 95% CI: 1.6–5.3), lower quantitative ultrasound measurements in bone (speed of sound: −27.9 m/s; 95% CI: −48.4 to −7.5), borderline lower diastolic blood pressure (−4.9 mmHg; 95% CI: −10.7–0.9), and significantly higher degradation products in urine (hydroxyproline/creatinine: 21.2 μmol/mmol; 95% CI: 2.3–40.1) as compared with asymptomatic hypermobile children of the total reference group (n = 16). After adjustment for possible confounders, children with generalized joint hypermobility without musculoskeletal complaints had a significantly higher total range of joint motion and more profound skin extensibility, as compared with the reference group (n = 79). Conclusions. Clinically manifested symptoms in otherwise healthy children with generalized joint hypermobility are accompanied by increases in the laxity of other body tissues. Thus, generalized joint hypermobility with musculoskeletal symptoms does not seem to be restricted to joint tissues. In symptomatic hypermobile children, a more systemic derangement was also present as compared with asymptomatic hypermobile children.