O\'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant genetic disorder caused by mutations in the KMT2E (lysine methyltransferase 2E) gene. The Third Xiangya Hospital of Central South University admitted a 12-year and 9-month-old male patient who presented with growth retardation, intellectual disability, and distinctive facial features. Peripheral blood was collected from the patient, and DNA was extracted for genetic testing. Chromosome karyotyping showed 46XY. Whole-exome sequencing and low-coverage massively parallel copy number variation sequencing (CNV-seq) revealed a 506 kb heterozygous deletion in the 7q22.3 region, which includes 6 genes, including KMT2E. The patient was diagnosed with ODLURO syndrome. Both the patient\'s parents and younger brother had normal clinical phenotypes and genetic test results, indicating that this deletion was a de novo mutation. The clinical and genetic characteristics of this case can help increase clinicians\' awareness of ODLURO syndrome.
O’Donnell-Luria-Rodan(ODLURO)综合征是KMT2E(lysine methyltransferase 2E)基因突变引起的常染色体显性遗传病。中南大学湘雅三医院收治1例表现为生长发育迟缓、智力低下、特殊面容的12岁9个月男性患儿，采集患者外周血，提取DNA进行基因检测，发现患儿染色体核型为46XY，全外显子组测序及低深度全基因组测序技术(low-coverage massively parallel copy number variation sequencing，CNV-seq)分析显示患儿在染色体7q 22.3区域存在506 kb的杂合性缺失，缺失区域包含KMT2E在内的6个基因，诊断为ODLURO综合征。其父母、弟弟临床表型及基因检测均无异常，提示该缺失为新发突变。此病例的临床和遗传特征有助于提高临床医师对ODLURO综合征的认识。.

Infantile systemic hyalinosis (ISH) is a very rare autosomal recessive disorder, which is characterized by a systemic build-up of hyaline material that causes extensive tissue destruction and functional impairment. The signs of this debilitating illness, which can involve organs, skin anomalies, and joint contractures, frequently appear in infancy. The paucity of available research on ISH emphasizes the need for all-encompassing management approaches to address the wide range of symptoms and enhance the overall quality of life for impacted babies. The interdisciplinary approach to ISH highlights the need for physiotherapy as a crucial element, with an emphasis on addressing the motor and developmental problems linked to the illness. Improving mobility and functional independence in newborns with ISH is facilitated by therapeutic exercises designed specifically for their needs. Here, we present a case of a six-month-old male child who visited a tertiary care center with complaints of minimal movements of all four limbs since birth with the inability to hold the neck. On examination, it was found that there were low-set ears with popular rashes and contractures over distal joints. Electromyography (EMG) and nerve conduction velocity (NCV) were done, which had abnormal findings suggestive of myopathy. On skin biopsy, it was confirmed that the child was suffering from ISH. Thus, the patient was referred to a physiotherapist. After six weeks of physiotherapy sessions, it was found that early and consistent physiotherapy interventions have been linked to a decrease in joint stiffness-related pain and discomfort, improving the affected infants\' general comfort. Furthermore, physiotherapy interventions have a crucial role in supporting adaptive methods to get around physical restrictions, making it easier for infants with ISH to reach developmental milestones that could otherwise be difficult. Although there is little research on the effects of physical therapy on infants with ISH, new data indicate that a proactive, tailored physical therapy program can greatly enhance the functional ability of impacted children, improve their overall quality of life, and avert further problems. It is crucial to incorporate physiotherapy into the comprehensive care of infants diagnosed with ISH. This highlights the significance of timely diagnosis, interdisciplinary cooperation, and continuous research aimed at improving and optimizing physiotherapeutic therapies for this uncommon and crippling genetic illness.

UNASSIGNED: The incidence of hip dislocation (HD) in arthrogryposis multiplex congenital ranges from 15 to 30 %. Besides a stable hip, the ambulation potential of an AMC child is also dependent on severity of associated knee and foot deformations. The primary objective of this review is to determine the proportion of ambulators in AMC children treated by open reduction for HD.
UNASSIGNED: We searched major electronic bibliographic databases for reports on the treatment of HD among AMC children. Based on the surgical approach for open reduction of HD in AMC children, we divided the included studies into groups 1 (Anterior approach open reduction) and 2 (Medial approach open reduction).
UNASSIGNED: We pooled 59 children/94 hips in this review from 7 studies. We identified 45 children/71 hips and 14 children/23 hips with a mean age of 20 (4-64) and 4.5 (0.5-11) months in groups 1 and 2, respectively. There were 97 % (44) and 92 %(Obeidat et al., 2011) 13 ambulators in groups 1 and 2, respectively. 47 % and 36 % of hips in groups 1 and 2 required additional procedures besides open reduction for redislocation and maintenance of hip reduction. 31 %22 and 13 %(Fisher et al., 1970 Feb) 3 of the hips sustained avascular necrosis in group 1 and 2.
UNASSIGNED: Children with AMC associated HD can be expected to ambulate with and without assistance in 90 % of the cases however, the foot and knee problems also need concomitant management. In children less than 6 months of age the medial approach based open reduction may be more efficacious and less complicating than anterior approach based open reduction however, at a later age anterior approach based open reduction is more effective due to need for pelvic and femur sided additional procedures.

BACKGROUND: The SLC29A3 gene, which encodes a nucleoside transporter protein, is primarily located in intracellular membranes. The mutations in this gene can give rise to various clinical manifestations, including H syndrome, dysosteosclerosis, Faisalabad histiocytosis, and pigmented hypertrichosis with insulin-dependent diabetes. The aim of this study is to present two Iranian patients with H syndrome and to describe a novel start-loss mutation in SLC29A3 gene.
METHODS: In this study, we employed whole-exome sequencing (WES) as a method to identify genetic variations that contribute to the development of H syndrome in a 16-year-old girl and her 8-year-old brother. These siblings were part of an Iranian family with consanguineous parents. To confirmed the pathogenicity of the identified variant, we utilized in-silico tools and cross-referenced various databases to confirm its novelty. Additionally, we conducted a co-segregation study and verified the presence of the variant in the parents of the affected patients through Sanger sequencing.
RESULTS: In our study, we identified a novel start-loss mutation (c.2T > A, p.Met1Lys) in the SLC29A3 gene, which was found in both of two patients. Co-segregation analysis using Sanger sequencing confirmed that this variant was inherited from the parents. To evaluate the potential pathogenicity and novelty of this mutation, we consulted various databases. Additionally, we employed bioinformatics tools to predict the three-dimensional structure of the mutant SLC29A3 protein. These analyses were conducted with the aim of providing valuable insights into the functional implications of the identified mutation on the structure and function of the SLC29A3 protein.
CONCLUSIONS: Our study contributes to the expanding body of evidence supporting the association between mutations in the SLC29A3 gene and H syndrome. The molecular analysis of diseases related to SLC29A3 is crucial in understanding the range of variability and raising awareness of H syndrome, with the ultimate goal of facilitating early diagnosis and appropriate treatment. The discovery of this novel biallelic variant in the probands further underscores the significance of utilizing genetic testing approaches, such as WES, as dependable diagnostic tools for individuals with this particular condition.

BACKGROUND: TTN is a complex gene with large genomic size and highly repetitive structure. Pathogenic variants in TTN have been reported to cause a range of skeletal muscle and cardiac disorders. Homozygous or compound heterozygous mutations tend to cause a wide spectrum of phenotypes with congenital or childhood onset. The onset and severity of the features were considered to be correlated with the types and location of the TTN variants.
METHODS: Whole-exome sequencing was performed on three unrelated families presenting with fetal akinesia deformation sequence (FADS), mainly characterized by reduced fetal movements and limb contractures. Sanger sequencing was performed to confirm the variants. RT-PCR analysis was performed.
RESULTS: TTN c.38,876-2 A > C, a meta transcript-only variant, with a second pathogenic or likely pathogenic variant in trans, was observed in five affected fetuses from the three families. Sanger sequencing showed that all the fetal variants were inherited from the parents. RT-PCR analysis showed two kinds of abnormal splicing, including intron 199 extension and skipping of 8 bases.
CONCLUSIONS: Here we report on three unrelated families presenting with FADS caused by four TTN variants. In addition, our study demonstrates that pathogenic meta transcript-only TTN variant can lead to defects which is recognizable prenatally in a recessive manner.

BACKGROUND H syndrome is an autosomal recessive disorder of histiocytic proliferation with clinical spectrum of unique cutaneous and systemic manifestations. There is no consistent treatment for the disease, and all available options are based on case reports. Here, we present the chronological progression of a case of H syndrome with typical cutaneous manifestations that was misdiagnosed early as meningitis-induced sensorineural hearing loss and later as a non-defined autoimmune connective tissue disease. A new tried, although failed, treatment option is described as well. CASE REPORT A 31-year-old Saudi woman born of a consanguineous marriage presented to our dermatology clinic with symmetrical indurated hyperpigmented to violaceous plaques over the medial thighs, upper legs, lower back, volar wrists, and upper arms, associated with hypertrichosis. Hallux valgus of the big toes was clinically detected as well. She had a history of sensorineural deafness, diabetes mellitus, chronic anemia, and hypothyroidism. Genetic analysis of the patient showed a homozygous frameshift pathogenic variant of the SLC29A3 gene, c.243del p.(Lys81Asnfs*20). Systemic treatments in the form of methotrexate and imatinib had been tried; however, both failed to control her sclerotic cutaneous changes. CONCLUSIONS Knowing the early life presentation and the variable clinical symptoms of H syndrome is crucial in early intervention and further prevention of the non-reversible changes. Moreover, avoiding unnecessary immunosuppressive medication use is warranted in certain circumstances.

UNASSIGNED: Cerebral palsy (CP) is the most common motor disability in children. The initial lesion to the developing brain may result in a myriad of neuromuscular comorbidities, including mobility deficiencies. The neuromuscular contributions to disability and rehabilitative frameworks specific to children with CP have been investigated separately. However, few reviews have examined the relationship between neuromuscular pathophysiology and rehabilitative frameworks among children with CP. Therefore, the purpose of this review was to investigate the impact of dynamic stretching orthoses and therapeutic exercise on range of motion (ROM), aerobic capacity, and mobility in relation to the neuromuscular contributions to disability in children with CP.
UNASSIGNED: Reviews of PubMed, Google Scholar, and Web of Science were conducted to identify literature focusing on the neuromuscular pathophysiology contributing to disability in children with CP and rehabilitative frameworks associated with this population. The search used a combination of keywords and subject headings to include \'cerebral palsy\', \'musculoskeletal\', \'neuromuscular\', \'spasticity\', \'rehabilitation\', \'exercise\', \'aerobic\', and \'orthosis\'. Selected manuscripts featured original cross-sectional and longitudinal research and meta-analyses.
UNASSIGNED: A total of 303 manuscripts were initially identified through search terms, with 182 articles excluded based on title and abstract evaluation, leaving 121 manuscripts for full-text analysis. Seven studies meeting the narrative review criteria were included. Evidence supporting the efficacy of dynamic stretching orthoses for improving lower extremity ROM is inconclusive. Aerobic and progressive resistive training may be beneficial for improving aerobic capacity and muscle strength in children with CP, which may result in enhanced mobility.
UNASSIGNED: Depending on the individual\'s clinical presentation, ROM and therapeutic exercise may be implemented to optimize function. Incorporating progressive resistive and aerobic exercises into a rehabilitation plan may improve mobility and aerobic capacity. As such, clinicians should consider resistance and aerobic exercise prescription as part of a long-term treatment plan for children with CP.

Joint contracture is one of the common diseases clinically, and joint capsule fibrosis is considered to be one of the most important pathological changes of joint contracture. However, the underlying mechanism of joint capsule fibrosis is still controversial. The present study aims to establish an animal model of knee extending joint contracture in rats, and to investigate the role of hypoxia-mediated pyroptosis in the progression of joint contracture using this animal model. 36 male SD rats were selected, 6 of which were not immobilized and were used as control group, while 30 rats were divided into I-1 group (immobilized for 1 week following 7 weeks of free movement), I-2 group (immobilized for 2 weeks following 6 weeks of free movement), I-4 group (immobilized for 4 weeks following 4 weeks of free movement), I-6 group (immobilized for 6 weeks following 2 weeks of free movement) and I-8 group (immobilized for 8 weeks) according to different immobilizing time. The progression of joint contracture was assessed by the measurement of knee joint range of motion, collagen deposition in joint capsule was examined with Masson staining, protein expression levels of HIF-1α, NLRP3, Caspase-1, GSDMD-N, TGF-β1, α-SMA and p-Smad3 in joint capsule were assessed using western blotting, and the morphological changes of fibroblasts were observed by transmission electron microscopy. The degree of total and arthrogenic contracture progressed from the first week and lasted until the first eight weeks after immobilization. The degree of total and arthrogenic contracture progressed rapidly in the first four weeks after immobilization and then progressed slowly. Masson staining indicated that collagen deposition in joint capsule gradually increased in the first 8 weeks following immobilization. Western blotting analysis showed that the protein levels of HIF-1α continued to increase during the first 8 weeks of immobilization, and the protein levels of pyroptosis-related proteins NLRP3, Caspase-1, GSDMD-N continued to increase in the first 4 weeks after immobilization and then decreased. The protein levels of fibrosis-related proteins TGF-β1, p-Smad3 and α-SMA continued to increase in the first 8 weeks after immobilization. Transmission electron microscopy showed that 4 weeks of immobilization induced cell membrane rupture and cell contents overflow, which further indicated the activation of pyroptosis. Knee extending joint contracture animal model can be established by external immobilization orthosis in rats, and the activation of hypoxia-mediated pyroptosis may play a stimulating role in the process of joint capsule fibrosis and joint contracture.

BACKGROUND: Bethlem Myopathy is a collagen VI-related myopathy presenting as a rare hereditary muscular disorder with progressive muscular weakness and joint contractures. Despite its milder clinical course relative to other myopathies, anaesthetic management can be challenging. High arched palates and fixed flexion deformities may contribute to a difficult airway. A progressive decline in pulmonary function can present later into adulthood. This respiratory decline can carry secondary cardiovascular consequences due to the progressive nature of restrictive lung disease, including right sided heart disease and pulmonary hypertension. We describe a case of a male patient with Bethlem Myopathy undergoing anaesthesia, to contribute to the limited body of literature on this condition and enhance awareness and guidance amongst anaesthesiologists on approaching patients with this condition. This is the first case report within the literature of its kind.
METHODS: This case details a 33-year-old male with Bethlem Myopathy undergoing tonsillectomy. Diagnosed in childhood following developmental delays, the patient had no prior anaesthetic exposure and no family history of anaesthetic complications. Anaesthetic induction was achieved without complications, avoiding depolarizing muscle relaxants and careful airway management. Extreme care was taken in patient positioning to prevent complications. The surgery proceeded without incident and muscle paralysis was reversed with Suggammadex, resulting in no adverse post-operative respiratory complications. The patient was discharged on the first post-operative day without any respiratory or cardiovascular compromise.
CONCLUSIONS: Bethlem Myopathy, while often exhibiting a mild clinical course, can present anaesthetic challenges. Awareness of potential complications including a difficult airway, cardiovascular and respiratory implications as well as the need for specialised monitoring and positioning is crucial to ensure a safe peri-operative course.

Burn injury and consequent contracture is not a new problem for humans. It is severely disabling for the patients, especially if it involves a large joint like the knee. The objective of the study was to evaluate the usefulness of the gastrocnemius flap and improvement in knee joint function following the use of the flap in post-burn flexion knee contracture. This prospective study was performed from January 2016 to December 2017. Twenty-five patients with flexion knee contracture were treated with incisional or excisional release of contracture and coverage with gastrocnemius muscle flap. The post operative improvement in knee function was evaluated. There was improvement in range of motion of the knee in all the operated patients and the patients were able to maintain unassisted bipedal locomotion. There was no flap loss in any case. In post-burn knee contracture with limited local fascio cutaneous flap options, gastrocnemius flap gives very good functional and aesthetic outcome with no major complication.
Les brûlures et leurs rétractions séquellaires sont bien connues. Ces rétractions peuvent être sévèrement handicapantes pour le patient, notamment lorsqu’elles sont situées sur des articulations importantes telles que le genou. Le but de cette étude est d’évaluer l’apport du lambeau de gastrocnemius sur la fonction du genou lors de son utilisation dans les rétractions séquellaires de brûlure. Cette étude prospective a été réalisée de janvier 2016 à décembre 2017. 25 patients avec des rétractions du genou ont été traités par incision ou excision de la cicatrice rétractile puis couverture par un lambeau musculaire de gastrocnemius. L’amélioration post-opératoire des mobilités du genou a été évaluée. Nous avons noté une amélioration des amplitudes articulaires du genou pour tous les patients et tous pouvaient déambuler en appui bipodal sans aide en post-opératoire. Nous n’avons perdu aucun lambeau. Dans les rétractions du genou, séquellaires de brûlure, avec peu de possibilités de lambeau facio-cutané local, le lambeau de gastrocnemius donne de bons résultats fonctionnels et cosmétiques sans complication majeure.