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Fibrodysplasia ossificans progressiva (FOP) is caused by an activating mutation in the Activin-Rezeptor 1 (ACVR1 / ALK2) Gene on Chromosome 2q23-24. Associated increased activity of the receptor predisposes to the development of heterotopic ossifications in the connective tissue, particularly in the muscles. The prevalence of the disorder is estimated to range between 1 in 1-2 Mio persons. At the time of birth, the only hallmark of the disease is a characteristic malformation of the great toe. During childhood, affected patients episodically develop painful soft tissue reactions, so-called flare-ups, marked by inflammation and swelling upon minor trauma. Subsequently these lesions form bone structures within the soft tissues by means of endochondral ossification. Typically, first lesions occur in the proximal, cranial, dorsal regions of the body, i. e. around the shoulder and the neck. Ossifications are irreversible and accumulate over time in the soft tissues, thereby progressively limiting patients' mobility. Increasing limitations of chest expansion eventually compromise respiratory capacity, promote the risk for pneumonia and right-sided heart failure. Therapeutic approaches focus on preventing additional trauma and interventions that might trigger additional heterotopic ossification, including avoidance of iatrogenic interventions like operations, biopsies and intramuscular injections. Supportive care comprises psychologic counseling, provision with appropriate technical tools as well as analgesic treatment, preferentially using NSAIDs. In case of a trauma, short term treatment with high doses of glucocorticoids is recommended in order to reduce the risk and extension of flare-ups and subsequent ossifications. Currently various novel therapeutic approaches are being evaluated. Among these, the retinoic acid receptor gamma (RARg) agonist Palovarotene is most advance in development. By binding to RARg, Palovarotene directly targets and interferes with the ALK2 in

Osteogenesis imperfecta (OI) is the most frequent hereditary bone disease during childhood. In most cases OI is caused by mutations affecting collagen production. Phenotypes of patients differ substantially and there is no clear genotype-phenotype correlation. Main symptom is an increased fracture rate due to inadequate traumata. Additionally, extra-skelettale signs like muscle hypotonia and hearing impairments are frequently reported. The multimodular therapy includes surgical procedures to treat fractures and to correct deformities. During childhood drug therapy is limited to the use of bisphosphonates. Other antiresorptive drugs like Denosumab are currently under investigation. After end of growth osteoanabolic agents like Teriparatide or Antisclerostin can be used. Most important is a regular training including physiotherapy and rehabilitation. To coordinate these therapies the care of the patients need to be centralized. Such a treatment in specialized centers will allow to learn more about natural history of the disease and to improve the care.

Hereditary skeletal disorders are rare but have a huge impact on patients and require a multidisciplinary medical care. A differentiation is made between diseases affecting bone matrix production (e. g. osteogenesis imperfecta) and those with defects in mineralization. The latter are separated into those where insufficient substrate is available (e. g. rickets) and those with a diminished function of alkaline phosphatase (e. g. hypophosphatasia). The diagnostics of diseases affecting collagen formation are mainly based on the clinical findings and radiographs, in comparison to mineralization defects where laboratory findings are important. Due to the complexity and diversity of the symptoms, therapy has to be undertaken by a multidisciplinary team coordinating all forms of treatment. For pediatric patients this is mostly localized in Sozial Padiatrischen Zentren. In most cases the medical treatment is purely symptomatic and the drugs used are neither approved nor internationally standardized; therefore, the off-label treatment should be conducted in specialized centers. The needs of patients are different during transition because in cases of synthesis defects with the culmination of growth and puberty a long period with few complaints begins and consequently a lack of contact with physicians, resulting in a loss of continuity of medical care. In contrast patients with mineralization defects need continuous medical care and there is a closer association with physicians; however, there are only relatively few physicians specialized in the treatment of adults and interdisciplinary treatment is not well established. A treatment structure similar to that in Sozial Padiatrischen Zentren would be desirable and in the future could be achieved by Centers for Rare Diseases.

Objectives: Jumping mechanography provides robust motor function indicators among healthy children. The aim of the study was to assess the reproducibility and validity of jumping mechanography conducted as single two-legged jump (S2LJ) in children with cerebral palsy (CP). Methods: 215 S2LJ investigations from a sample of 75 children with CP were eligible for evaluation. For the estimation of the reproducibility, only the baseline set of data per patient were used. Gross motor function was evaluated by the Gross Motor Function Measure (GMFM-66). In 135 S2LJ investigations, GMFM66 was assessed within a week in the same child. This data was used for validity assessment. Results: Coefficients of variation for the main outcome parameters ranged between 6.15-9.71%, except for jump height (CV%=27.3%). The intraclass correlation coefficients for peak velocity (V-max) and peak power relative to body weight (P-max/mass) was 0.927 and 0.931. V-max and P-max/mass were also the test parameters with the strongest correlation to the GMFM-66 score (>0.7). Conclusions: S2LJ assessed in the present study provided reproducible outcome measures particularly for V-max and P-max/mass in children with CP. Further, V-max and P-max/mass showed the strongest correlation with the GMFM-66 score and seem to be the most relevant evaluation criteria.

Objectives: The aim of this study was to evaluate the effect of scoliosis specific exercises (SSE) on a side-alternating whole body vibration platform (sWBV) as a home-training program in girls with adolescent idiopathic scoliosis (AIS). Methods: 40 female AIS patients (10-17 years) wearing a brace were randomly assigned to two groups. The intervention was a six months, home-based, SSE program on a sWBV platform five times per week. Exercises included standing, sitting and kneeling. The control group received regular SSE (treatment as usual). The Cobb angle was measured at start and after six months. Onset of menarche was documented for sub-group analysis. Results: The major curve in the sWBV group decreased significantly by -2.3 degrees (SD +/- 3.8) (95% CI -4.1 to -0.5; P=0.014) compared to the difference in the control group of 0.3 degrees (SD +/- 3.7) (95% CI -1.5 to 2.2; P=0.682) (P=0.035). In the sWBV group 20% (n=4) improved, 75% (n=15) stabilized and 5% (n=1) deteriorated by >= 5 degrees. In the control group 0% (n=0) improved, 89% (n=16) stabilized and 11% (n=2) deteriorated. The clinically largest change was observed in the 'before-menarche' sub-group. Conclusions: Home-based SSE combined with sWBV for six months counteracts the progression of scoliosis in girls with AIS; the results were more obvious before the onset of the menarche.

Objectives: to investigate feasibility, safety and efficacy of home-based side-alternating whole body vibration (sWBV) to improve motor function in toddlers with cerebral palsy (CP). Methods: Randomized controlled trial including 24 toddlers with CP (mean age 19 months (SD+3.1); 13 boys). Intervention: 14 weeks sWBV with ten 9-minute sessions weekly (non-individualized). Group A started with sWBV, followed by 14 weeks without; in group B this order was reversed. Feasibility (>= 70% adherence) and adverse events were recorded; efficacy evaluated with the Gross Motor Function Measure (GMFM-66), Pediatric Evaluation of Disability Inventory (PEDI), at baseline (T0), 14 (T1) and 28 weeks (T2). Results: Developmental change between T0 and T1 was similar in both groups; change scores in group A and B: GMFM-66 2.4 (SD+2.1) and 3.3 (SD+2.9) (p=0.412); PEDI mobility 8.4 (SD+6.6) and 3.5 (SD+9.2) (p=0.148), respectively. In two children muscle tone increased post-sWBV. 24 children received between 67 and 140 sWBV sessions, rate of completed sessions ranged from 48 to 100% and no dropouts were observed. Conclusion: A 14-week home-based sWBV intervention was feasible and safe in toddlers with CP, but was not associated with improvement in gross motor function.

Objectives: Osteogenesis imperfecta (OI) is a rare hereditary disease leading to bone fragility. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. Aim of this study was a 48-week, open-label, pilot study of the safety and efficacy of denosumab in 10 children with OI. Methods: Ten patients (age range: 5.0-11.0 years; at least two years of prior bisphosphonate treatment) with genetically confirmed OI were studied. Denosumab was administered subcutaneously every 12 weeks with 1 mg/kg body weight. Primary endpoint was change of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 48 weeks. Safety was assessed by bone metabolism markers and adverse event reporting. Results: Mean relative change of lumbar aBMD was +19 % (95%-CI: 7-31%). Lumbar spine aBMD Z-Scores increased from -2.23 +/- 2.03 (mean +/- SD) to -1.27 +/- 2.37 (p=0.0006). Mobility did not change (GMFM-88 +2.72 +/- 4.62% (p=0.16); one-minute walking test +11.00 +/- 15.82 m (p=0.15). No severe side effects occurred. Conclusions: On average, there was a significant increase in lumbar spine aBMD percent change after 48 weeks of denosumab. There was no change in mobility parameters and no serious adverse events. Further trials are necessary to assess long-term side effects and efficacy.