The origin of contractures in spastic forms of cerebral palsy (CP) is unclear. Tomorrow the early appearance and persistence of spasticity are not qualified as the main reason of growths disturbances, musculo-skeletal system deformations and secondary orthopedic complications. The latest investigations have shown prominent changes in the spastic muscles on the different structural levels and stages of muscle development. This study describes the histological, morphological, and biomechanical changes in the spastic muscles that play a pathophysiological role in the formation of CP contractions. The authors discuss the changes in the muscle fiber size, differentiation and elastic properties, degrees of the lengthening resistance in the bundles of muscle fibers, extracellular matrix proliferation, structural and mechanical changes, disturbances in gene expression and regulation in the tendons and muscle tissue, changes in the length and number of sarcomers, as well as the length and cross-section of the whole muscle. Therefore, the movement limitations and contractions in CP do not depend on one universal mechanism. It is a combination of different structural changes in the muscles and the failure of the central movement and postural control.

In all patients with mucopolysaccharidosis type I (MPS I), skeletal disease (dysostosis multiplex) is a prominent, debilitating, condition related complication that may impact strongly on activities of daily living. Unfortunately, it is not alleviated by treatment with hematopoietic cell transplantation (HCT) or enzyme replacement therapy (ERT). Although early kyphosis is one of the key features of dysostosis multiplex, there is no international consensus on the optimal management. Therefore, an international consensus procedure was organized with the aim to develop the first clinical practice guideline for the management of thoracolumbar kyphosis in MPS I patients. A literature review was conducted to identify all available information about kyphosis and related surgery in MPS I patients. Subsequently, a modified Delphi procedure was used to develop consensus statements. The expert panel included 10 spinal orthopedic surgeons, 6 pediatricians and 3 physiotherapists, all experienced in MPS I. The procedure consisted of 2 written rounds, a face-to-face meeting and a final written round. The first 2 rounds contained case histories, general questions and draft statements. During the face-to-face meeting consensus statements were developed. In the final round, the panel had the opportunity to anonymously express their opinion about the proposed statements. Eighteen case series and case reports were retrieved from literature reporting on different surgical approaches and timing of thoracolumbar kyphosis surgery in MPS I. During the face-to-face meeting 16 statements were discussed and revised. Consensus was reached on all statements. This international consensus procedure resulted in the first clinical practice guideline for the management of thoracolumbar kyphosis in MPS I patients, focusing on the goals and timing of surgery, as well as the optimal surgical approach, the utility of bracing and required additional assessments (e.g. radiographs). Most importantly, it was concluded that the decision for surgery depends not only on the kyphotic angle, but also on additional factors such as the progression of the deformity and its flexibility, the presence of symptoms, growth potential and comorbidities. The eventual goal of treatment is the maintenance or improvement of quality of life. Further international collaborative research related to long-term outcome of kyphosis surgery in MPS I is essential as prognostic information is lacking.

Purpose: Cleidocranial dysplasia is an autosomal dominant disorder characterized by defective ossification of the intramembraneous ossification (primarily the clavicles, cranium, and pelvis), and it is caused by mutations in the RUNX2 gene that is responsible for osteoblast differentiation. Spine deformities were of progressive nature and considered to be the major orthopedic abnormalities encountered in our practice in patients with cleidocranial dysplasia. We aimed to further delineate the underlying spine pathology and its etiological understanding. Extraspinal deformities were dealt with respectively. Material and Methods: In this paper, we describe 7 patients who were consistent with the phenotypic and the genotypic characterization of cleidocranial dysplasia. Reformatted computed tomography (CT) scans have been applied in several instances to further understand the underlying pathology of progressive spine tilting. Radiographs were sufficient to illustrate other skeletal malformations. Results: Anatomical survey demonstrates that a broad spectrum of frequently unrecognized orthopedic aberrations were encountered. We believe that torticollis has evolved in connection with the persistence of synchondrosis of the skull base and the upper cervical spine and these are strongly correlated to the well-known pathology of posterior occipital synchondrosis. Similarly, scoliosis and kyphoscoliosis resulted from the pathologic aberration of the cartilaginous stage of disrupted embryological development. All our results are discussed for the first time. Coxa vara, patellar dysplasia, and genu valgum were observed as extraspinal deformities. Conclusion: This paper includes for the first time the anatomical analysis of the malformation complex of the craniocervical and the entire spine in patients with cleidocranial dysplasia. Reformatted CT scan was the modality of choice. We were able to illustrate that the persistence of skull base and the cervical spine synchondrosis were correlated with the pathological mechanism of the posterior occipital synchondrosis. Therefore, injuries to the craniocervical region in these patients might lead to a wide range of dreadful complications, ranging from complete atlanto-occipital or atlanto-axial dislocation to nondisplaced occipital condyle avulsion fractures with the possibility of morbid and or mortal outcome. On the other hand, the persistence of a cartilaginous spine was the reason behind the progressive spine tilting. This pathological form can be considered as a notoriously unpredictable malformation complex. The value of presenting these patients is to demonsterate that the genotype is not a precise index to assess the severity and the natural history of the phenotype.

The significant variability in the clinical manifestations of COL2A1-associated skeletal dysplasias makes it necessary to conduct a clinical and genetic analysis of individual nosological variants, which will contribute to improving our understanding of the pathogenetic mechanisms and prognosis. We presented the clinical and genetic characteristics of 60 Russian pediatric patients with type II collagenopathies caused by previously described and newly identified variants in the COL2A1 gene. Diagnosis confirmation was carried out by new generation sequencing of the target panel with subsequent validation of the identified variants using automated Sanger sequencing. It has been shown that clinical forms of spondyloepiphyseal dysplasias predominate in childhood, both with more severe clinical manifestations (58%) and with unusual phenotypes of mild forms with normal growth (25%). However, Stickler syndrome, type I was less common (17%). In the COL2A1 gene, 28 novel variants were identified, and a total of 63% of the variants were found in the triple helix region resulted in glycine substitution in Gly-XY repeats, which were identified in patients with clinical manifestations of congenital spondyloepiphyseal dysplasia with varying severity, and were not found in Stickler syndrome, type I and Kniest dysplasia. In the C-propeptide region, five novel variants leading to the development of unusual phenotypes of spondyloepiphyseal dysplasia have been identified.

Multiple epiphyseal dysplasias (MED) are a clinically and genetically heterogeneous group of skeletal dysplasias with a predominant lesion in the epiphyses of tubular bones. Variants in the SLC26A2 gene cause their autosomal recessive form (rMED or MED type 4). The accumulation of data regarding the genotype–phenotype correlation can help in the diagnosis and proper management of these patients. The aim of this study was to survey the clinical and genetic characteristics of 55 patients with MED type 4 caused by variants in the SLC26A2 gene. Diagnosis confirmation was carried out by radiography and custom panel sequencing consisting of 166 genes responsible for the development of hereditary skeletal pathology. This was followed by the validation of the identified variants using automated Sanger sequencing (for six patients) and the direct automatic Sanger sequencing of the coding sequence and the adjacent intron regions of the SLC26A2 gene for 49 patients. Based on the clinical and genetic analysis of our sample of patients, two main MED type 4 phenotypes with early and late clinical manifestations were identified. An early and more severe form of the disease was observed in patients with the c.835C > T variant (p.Arg279Trp), and the late and milder form of the disease was observed in patients with the c.1957T > A variant (p.Cys653Ser) in the homozygous or compound heterozygous state with c.26 + 2T > C. It was also shown that only three pathogenic variants were found in 95.3% of the alleles of Russian patients with MED type 4: c.1957T > A (p.Cys653Ser), c.835C > T (p.Arg279Trp), and c.26 + 2T > C; thus, it can be assumed that the primary analysis of these variants will contribute to the optimal molecular genetic diagnostics of MED type 4.

BACKGROUND: Congenital malformations of the spine and spinal cord can be combined with various clinical manifestations of the spine, spinal cord, and lower extremities. Children with these neurological disorders often lack sensitivity and motor activity of their lower extremities and, in most cases, have bladder infections and incontinence (lack of bladder and bowel control). AIM: This study aims to analyze publications with the diagnostic and treatment results of patients with neurological, orthopedic, neurological, and ophthalmological problems with spina bifida. MATERIALS AND METHODS: We searched PubMed, Web of Science, Scopus, MEDLINE, eLibrary, and RSCI databases and found about 2000 references and 374 articles. We selected 60 articles for review in orthopedics, neurosurgery, urology, and ophthalmology. RESULTS: Neural tube defects are a wide range of congenital malformations, including skull defects and open or closed spinal dysraphism. The incidence of spine and spinal cord malformations in different countries is quite broad and amounts to 0.3199.4 cases per 10,000 births worldwide. Spinal cord malformations often occur in combination with bladder infections and incontinence, limb deformities, and other central nervous system developmental anomalies. Among the orthopedic problems leading to impaired support function, the most common are foot deformities and hip joint instability. Orthopedic monitoring of a patient with spina bifida consists of mainly preventing or correcting deformities according to the rehabilitation potential of the child. The timely completion of treatment allows the child to maintain mobility and independence of movement daily activities. At the same time, such treatment must pursue realistic goals according to the potential motor level of the child. In addition to neurosurgical and orthopedic problems, most children with spina bifida (88%94%) suffer from pelvic disorders. A urologist should observe a patient with spina bifida to perform ultrasound and laboratory monitoring of both the lower and upper urinary tract conditions from an early age. Timely procedures to eliminate urinary retention and sanitation can maintain normal kidney function and contribute to the adequate conduct of motor and neurological rehabilitation of the child. The most common complication of spina bifida is the Chiari II malformation, which is manifested by damage to brain stem structures and internal occlusal hydrocephalus with various symptoms, including neuroophthalmological signs. CONCLUSIONS: A multidisciplinary team of specialists comprising a neurologist, neurosurgeon, urologist, orthopedic surgeon, ophthalmologist, orthosis specialist, and psychologist should be involved in treating the children with the above presented problems. The use of an integrated approach to treat this group is absolutely justified and enabled the maximum rehabilitation potential of the child to be achieved.