Skeletal Deformities Research Articles

Pathophysiological Investigation of Skeletal Deformities of Musculocontractural Ehlers-Danlos Syndrome Using Induced Pluripotent Stem Cells.

Musculocontractural Ehlers-Danlos syndrome caused by mutations in the carbohydrate sulfotransferase 14 gene (mcEDS-CHST14) is a heritable connective tissue disorder characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral, and ocular systems. Progressive skeletal deformities are among the most frequent and serious complications affecting the quality of life and activities of daily living in patients. After establishing induced pluripotent stem cells (iPSCs) from cultured skin fibroblasts of three patients with mcEDS-CHST14, we generated a patient iPSC-based human osteogenesis model and performed an in vitro assessment of the phenotype and pathophysiology of skeletal deformities. Patient-derived iPSCs presented with remarkable downregulation of osteogenic-specific gene expression, less alizarin red staining, and reduced calcium deposition compared with wild-type iPSCs at each stage of osteogenic differentiation, including osteoprogenitor cells, osteoblasts, and osteocytes. These findings indicated that osteogenesis was impaired in mcEDS-CHST14 iPSCs. Moreover, the decrease in decorin (DCN) expression and increase in collagen (COL12A1) expression in patient-derived iPSCs elucidated the contribution of CHST14 dysfunction to skeletal deformities in mcEDS-CHST14. In conclusion, this disease-in-a-dish model provides new insight into the pathophysiology of EDS and may have the potential for personalized gene or drug therapy.

Rehabilitation of severe dentofacial deformity after early radiotherapy of retinoblastoma: a case report

BackgroundRetinoblastoma is an intraocular cancer of infancy and childhood, which has been treated with radiation therapy and chemotherapy. Radiation on growing patients can cause deterioration in maxillofacial growth and development that leads to severe skeletal discrepancies between the maxilla and mandible, and dental problems such as crossbite, openbite, and hypodontia.Case presentationWe present the case of a 19-year-old Korean man with chewing disability and dentofacial deformities. He had undergone enucleation of the right eye and radiation therapy of the left eye due to retinoblastoma 100 days after birth. Subsequently, he received cancer therapy for the secondary nasopharyngeal cancer at the age of 11 years. He was diagnosed with severe skeletal deformity including sagittal, transverse, and vertical growth deficiency of the maxilla and midface, and with class III malocclusion, severe anterior and posterior crossbite, posterior openbite, multiple missing upper incisors, right premolars, and second molars, and impaction of the lower right second molars. To restore impaired functions and esthetics of the jaw and dentition, the orthodontic treatment combined with two jaw surgery was performed. At the end of surgical orthodontics, dental implants were placed for prosthetic treatment of missing teeth. Additional plastic surgery for zygoma elevation was done with calvarial bone graft followed by fat graft. Facial esthetics and occlusal functions of patient were favorably enhanced with the improvement of skeletal discrepancy and the rehabilitation of maxillary dentition by prosthetic work. At the 2-year follow-up, the skeletal and dental relationships and implant prosthetics were well maintained.ConclusionIn an adult patient with dentofacial deformities caused by early cancer therapy in the head and neck area, interdisciplinary interventions including additional plastic surgery of zygoma depression and prosthetic work of missing teeth as well as surgical–orthodontic treatment could establish favorable facial esthetics and oral rehabilitation.

Sagliker Syndrome – A Case Report

Aim: To present a case of Sagliker syndrome (SS), a rare syndrome caused by longterm heavy tertiary hyperparathyroidism (HPT) in end-stage renal disease (ESRD). Case report: In the year 2000, the 38-year-old man was diagnosed with ESRD. He is currently of low height, paraplegic, pigeon and barrel chested, with elongated upper extremities, deformed fingers, mandibular and maxillary asymmetric deformities with teeth malformations. Due to extremely high serum parathormone (PTH), resistant to pharmacological treatment, subtotal parathyroidectomy (PTx) was performed in 2007. However, he underwent parathyroid resurgery in 2010 for persistently high PTH of more than 2500 pg/mL (upper normal limit 69). In 2012, imaging found two suspected parathyroid glands and one of them was surgically removed. Postoperatively, the expected decrease in calcium and PTH serum concentrations did not occur. Ten years after the diagnosis of ESRD, the patient began to notice more pronounced skeletal deformities (upper, lower jaw, extremities, deformities of fingers, kyphoscoliosis) along with depressive disorder. Laboratory findings still show extremely high PTH (1994 pg/mL), low calcium, 1.89 mmol/L (normal range 2.14–2.53), and high alkaline phosphatase, 837 U/L (normal range 60–120), despite continuous pharmacological treatment. Conclusion: SS was firstly recognized by Yahya Sagliker in 2004 and it has not been described in Croatia to date. Pervasiveness and knowledge of the syndrome is still poor. The most efficient way of treating/preventing SS is early total PTx in severe secondary HPT related to ESRD. However, it can only stop progress of the disease, but cannot return skeletal deformities.

A rare case of Coffin–Lowry syndrome accompanied by a copper-beaten skull appearance

Coffin-Lowry syndrome (CLS), usually a result of loss-of-function mutations in the RPS6KA3 gene located at Xp22.2, is a very rare genetic condition. It is associated with different phenotypes, including dysmorphic facial features, neuro-developmental impairment, short stature, and skeletal deformities. Here we describe a four-year-old boy who had distinct clinical features of CLS: moderate mental and motor retardation, brachycephaly, microcephaly, hypertelorism, low-set and prominent ears, down- slanted palpebral fissures, a depressed nasal bridge with thick nasal alae and septum, a high-arched palate, widely spaced teeth, and retrognathia. Genetic analysis revealed a pathogenic variant in the RPS6KA3 gene, NM_004586.3: exon 22: c.2186G>A: (p.Arg729Gln). His healthy mother was a heterozygous carrier of the variant. In addition to the clinical findings, the patient’s X-ray revealed a very rare feature of a copper-beaten skull appearance. The link between CLS and a copper-beaten skull has never been reported before. This case demonstrates the variability in presentation of CLS and signifies the association of a rare radiographic finding of copper-beaten skull with CLS. Based on this case, we recommend screening skull radiographs at the clinic for copper-beaten skulls in patients with CLS.

Reorientation methodology for reproducible head posture in serial cone beam computed tomography images

Low dose and accessibility have increased the application of cone beam computed tomography (CBCT). Often serial images are captured for patients to diagnose and plan treatment in the craniofacial region. However, CBCT images are highly variable and lack harmonious reproduction, especially in the head’s orientation. Though user-defined orientation methods have been suggested, the reproducibility remains controversial. Here, we propose a landmark-free reorientation methodology based on principal component analysis (PCA) for harmonious orientation of serially captured CBCTs. We analyzed three serial CBCT scans collected for 29 individuals who underwent orthognathic surgery. We first defined a region of interest with the proposed protocol by combining 2D rendering and 3D convex hull method, and identified an intermediary arrangement point. PCA identified the y-axis (anterioposterior) followed by the secondary x-axis (transverse). Finally, by defining the perpendicular z-axis, a new global orientation was assigned. The goodness of alignment (Hausdorff distance) showed a marked improvement (> 50%). Furthermore, we clustered cases based on clinical asymmetry and validated that the protocol was unaffected by the severity of the skeletal deformity. Therefore, it could be suggested that integrating the proposed algorithm as the preliminary step in CBCT evaluation will address a fundamental step towards harmonizing the craniofacial imaging records.

An unusual case of familial hypophosphatemic rickets

Rickets is the failure of mineralisation of osteoid and newly formed bones in a child skeleton. It is commonly associated with vitamin D deficiency; however, it can be because of a decrease in serum phosphate level leading to inadequate mineralization of cartilage and bone, consequent skeletal deformities and growth retardation. In hypophosphatemic rickets, there are both inherited and acquired forms, where X-linked hypophosphatemic rickets (XLH) is the most prevalent genetic form and caused by mutations in the phosphate-regulating endopeptidase (PHEX) gene. XLH is associated with growth retardation and bone deformities. This rare variety was diagnosed in a 2 year 4 month old child who had brought by parents with complaint of abnormal gait. In the present case, clinical and radiographic aspects of manifestation of familial hypophosphatemic rickets are discussed.

Osteo-pathological analysis provides evidence for a survived historical ship strike in a Southern Hemisphere fin whale (Balaenoptera physalus).

The life history of a fin whale (Balaenoptera physalus) caught during whaling operations in the 1950s was partly reconstructed. 3D surface models of the bones of the skeleton curated at the Zoological Museum of Hamburg were used for an osteopathological analysis. The skeleton revealed multiple healed fractures of ribs and a scapula. Moreover, the processus spinosi of several vertebrae were deformed and arthrosis was found. Together, the pathological findings provide evidence for large blunt trauma and secondary effects arising from it. Reconstruction of the likely cause of events suggests collision with a ship inflicting the fractures and leading to post traumatic posture damage as indicated by skeletal deformations. The injured bones had fully healed before the fin whale was killed by a whaler in the South Atlantic in 1952. This study is the first in-detail reconstruction of a historical whale-ship collision in the Southern Hemisphere, dating back to the 1940s, and the first documentation of a healed scapula fracture in a fin whale. The skeleton provides evidence for survival of a ship strike by a fin whale with severe injuries causing long-term impairment.

Systematic review of health related-quality of life in adults with osteogenesis imperfecta

BackgroundOsteogenesis imperfecta (OI) is a rare, connective tissue disorder characterised by bone fragility, resulting in recurrent fractures and skeletal deformities. Extra-skeletal manifestations include dentinogenesis imperfecta, hearing abnormalities and lung disease. These co-morbidities combined with recurrent fractures can exert a significant impact on health-related quality of life (HR-QOL). It is important to assess HR-QOL throughout adulthood because the prevalence of some OI-specific complications increases with age.MethodsPubMed, EMBASE and CENTRAL databases were searched on 2nd February 2022 to identify studies reporting quantitative assessments of HR-QOL in adults with OI. The primary endpoint was to determine the impact of an OI diagnosis on adult’s HR-QOL. Secondary endpoints were to (i) examine how frequently various HR-QOL assessment tools were used (ii) identify differences in HR-QOL between OI types and (iii) investigate the determinants of HR-QOL in adults with OI. Search results were exported to Endnote where two reviewers independently conducted title/abstract and full-text reviews. Data from accepted studies were extracted into Microsoft Excel. A narrative synthesis was then undertaken.ResultsThe review identified 17 studies with a total of 1,648 adults. The Short Form-36 (SF-36) was the most frequently reported HR-QOL assessment tool and was used in nine studies. Physical HR-QOL was reduced in adults with OI. Physical component scores (PCS) or individual physical domains of the SF-36 were lower in eight of nine studies. Mental component scores (MCS) were preserved in all six studies, however individual mental health domains of the SF-36 were reduced in some studies. The prevalence of anxiety/depression was relatively low in adults with OI. Those with type III OI had lower physical and respiratory HR-QOL but preserved mental HR-QOL compared with type I. The prevalence of fatigue and pain was higher in adults with OI compared with reference populations. Age and cardio-pulmonary co-morbidities were associated with lower HR-QOL.ConclusionOI in adulthood has a wide-ranging negative impact on HR-QOL. Physical and respiratory HR-QOL were lower, while the prevalence of pain and fatigue were higher than in reference populations. Mental HR-QOL was relatively preserved, although some deficits were identified. Age and cardio-pulmonary co-morbidities were associated with lower HR-QOL.

NEFL-Related Charcot-Marie Tooth Disease due to P440L Mutation in Two Italian Families: Expanding the Phenotype and Defining Modulating Factors

Introduction: Mutations in the neurofilament polypeptide light chain (NEFL) gene account for <1% of all forms of Charcot-Marie-Tooth (CMT) diseases and present with different phenotypes, including demyelinating, axonal and intermediate neuropathies, and with diverse pattern of transmission, with dominant and recessive inheritance being described. Methods: Here, we present clinical and molecular data in two new unrelated Italian families, affected with CMT. Results: We studied fifteen subjects (11 women, 4 men), age range 23–62 year. Onset of symptoms was mainly in childhood, with running/walking difficulties; some patients were pauci-asymptomatic; almost all shared variably distributed features of absent/reduced deep tendon reflexes, impaired gait, reduced sensation, and distal weakness in the legs. Skeletal deformities were seldom documented and were of mild degree. Additional features included sensorineural hearing loss in 3 patients, underactive bladder in 2 patients, and cardiac conduction abnormalities, requiring pacemaker implantation, in one child. Central nervous system (CNS) impairment was not documented in any subject. Neurophysiological investigation disclosed feature suggestive of demyelinating sensory-motor polyneuropathy in one family and resembling an intermediate form in the other. Multigene panel analysis of all known CMT genes revealed two heterozygous variants in NEFL: p.E488K and p.P440L. While the latter change segregated with the phenotype, the p.E488K variant appeared to act as a modifier factor being associated with axonal nerve damage. Conclusions: CMT related to P440L mutation in NEFL is associated with a mild, childhood-onset phenotype, showing prevalently sensory distal limbs involving and with motor impairment predominantly involving anterolateral leg muscles, in the absence of CNS involvement. Additional findings, never reported so far in patients with NEFL mutation, are cardiological and urinary dysfunctions. Our study expands the array of clinical features associated with NEFL-related CMT.

Down syndrome patients with normal hearts: are they really normal?

Even though congenital heart disease is a common finding in down syndrome (DS) patients, some of them have anatomically normal hearts. However, the term "normal" might not be suitable, as these patients usually suffer from functional cardiac dysfunction. Several research highlighted that despite the absence of anatomical heart defects, subtle cardiac function derangements are present in DS patients. We aim to assess cardiac functions by Two-dimensional echocardiography and tissue Doppler imaging (TDI) in pediatric DS patients who have anatomically normal hearts. One hundred seventy-two patients with karyotyping confirmed DS with anatomically normal hearts and 165 healthy normal control children were enrolled in the current study. Their cardiac functions were assessed using both 2-dimensional echocardiography and TDI. Both patients and controls had structurally and anatomically normal hearts. In DS patients, the right side of the heart showed a significant reduction in both systolic and diastolic functions. Systolic dysfunction was evident by significantly decreased levels of Tricuspid annular plane systolic excursion and systolic wave by TDI. Diastolic dysfunction of the right ventricle was evident by prolonged deceleration time by conventional echocardiography and a significant decrease in annular tissue doppler velocity during early diastole/late diastole ratio by TDI. The E/De ratio was significantly increased. Even with anatomically normal hearts, DS patients should undergo cardiac function assessment by echocardiography & TDI. TDI is superior to conventional echocardiography in detecting subtle cardiac dysfunction especially left ventricular diastolic dysfunction in DS patients. TDI showed a significant decrease in the early/atrial ratio of mitral valve annulus and prolongation of left ventricle isometric relaxation time in DS children. Also, the left ventricle E/De ratio was prolonged denoting elevated filling pressures and diastolic dysfunction. This indicates that the TDI has higher sensitivity to detect diastolic dysfunction than conventional Echocardiography. Biventricular TDI-derived myocardial performance index was found to be significantly increased in DS children.

Chloroacetonitrile reduces rat prenatal bone length and induces oxidative stress, apoptosis, and DNA damage in rat fetal liver.

One of the disinfection byproducts of chlorinating drinking water is chloroacetonitrile (CAN). Thirty-six female rats were used and distributed equally into four groups. The low dose treated group received CAN at a dose of 5.5mg/kg body weight/day (1/40 LD50 ) orally from the 6th to 12th day of gestation. The high dose treated group received 11 mg/kg body weight/day (1/20 LD50 ) of CAN orally for the same period, the vehicle control group received 1mL of corn oil, and the water control group received 1mL of distilled water orally for the same period. High dose exposure to CAN significantly reduced gravid uterine weight, fetal body weights, and length, and caused obvious skeletal deformities, weak mineralization. Fetal tibial growth plates displayed histopathologic changes. Induced oxidative stress and redox imbalance in fetal liver tissues was evidenced by significantly decreased in catalase and superoxide dismutase activity, and elevated malondialdehyde levels. Histopathological, glycogen content changes, and DNA damage were observed in the fetal liver of high dose treated group. Additionally, administration of high dose of CAN induced apoptosis, evidenced by increased caspase-3 concentration in fetal liver. Thus, extensive exposure to CAN induces poor pregnancy outcomes. CAN levels in water should be monitored regularly.

Distinguishing the Effects of Water Volumes versus Stocking Densities on the Skeletal Quality during the Pre-Ongrowing Phase of Gilthead Seabream (Sparus aurata).

Gilthead seabream (Sparus aurata) production is a highly valued aquaculture industry in Europe. The presence of skeletal deformities in farmed gilthead seabream represents a major bottleneck for the industry leading to economic losses, negative impacts on the consumers' perception of aquaculture, and animal welfare issues for the fish. Although past work has primarily focused on the hatchery phase to reduce the incidence of skeletal anomalies, this work targets the successive pre-ongrowing phase in which more severe anomalies affecting the external shape often arise. This work aimed to test the effects of: (i) larger and smaller tank volumes, stocked at the same density; and (ii) higher and lower stocking densities maintained in the same water volume, on the skeleton of gilthead seabream fingerlings reared for ~63 days at a pilot scale. Experimental rearing was conducted with gilthead seabream juveniles (~6.7 ± 2.5 g), which were selected as 'non-deformed' based on external inspection, stocked at three different densities (Low Density (LD): 5 kg/m3; Medium Density (MD): 10 kg/m3; High Density (HD): 20 kg/m3) in both 500 L and 1000 L tanks. Gilthead seabream were sampled for growth performance and radiographed to assess the skeletal elements at the beginning and end of the experimental trial. Results revealed that (i) LD fish were significantly longer than HD fish, although there were no differences in final weights, regardless of the water volume; (ii) an increase in the prevalence of seabream exhibiting cranial and vertebral axis anomalies was found to be associated with increased density. These results suggest that farmers can significantly reduce the presence of some cranial and axis anomalies affecting pre-ongrown gilthead seabream by reducing the stocking density.

Finding Yaws among Indigenous People: Lessons from Case Detection Surveys in Luzon and Visayas Island Groups of the Philippines.

Yaws is a chronic, highly contagious skin and bone infection caused by Treponema pallidum subspecies pertenue, usually affecting children in impoverished and remote communities. Yaws lesions have thick yellow crusts on pink papillomas that ulcerate and leave deep scars. Yaws cases were confirmed in the Liguasan Marsh, Mindanao Island group, Southern Philippines, in 2017, but there were no cases confirmed in the Luzon and Visayas Island groups. We aimed to detect at least one active or latent yaws case in the island groups of Luzon and Visayas. Active yaws surveillance was conducted by inviting healthcare providers to report yaws suspects. Five remote villages were included in the case detection surveys: three in Luzon and two in the Visayas Island groups. Two indigenous peoples communities were included: Aetas of Quezon and Dumagat/Remontados of Rizal provinces. Trained field personnel conducted free skin check-ups of children, household contacts, and community members. Yaws suspects underwent point-of-care serologic tests for T. pallidum and nontreponemal antibodies. A total of 239 participants were screened for skin diseases, and 103 had serologic tests. Only the Aetas of Quezon province, Luzon, had confirmed yaws cases. Nineteen cases (54.3%) were detected among 35 Aetas: five active yaws (four children, one adult), two latent yaws (adults), and 12 past yaws (1 child, 11 adults). An 8-year-old boy had yaws with skeletal deformities. We report the first yaws cases among the Aetas of Quezon, Luzon Island group. Active yaws surveillance and case detection in remote areas and among indigenous peoples should continue.

Cross malformations and Histolgical Changes in Brain and Eyes of Mice and Their Embryos Exposed to Glue smoke

Histological changes were detected in brain and eyes of female mice and their embryos as a result of exposure to the doses1500,2500 and 3500mg/kg body weight) of glue smoke given during the7th day of pregnancy as till the18th day of pregnancy. Data of behavioral changes were recorded of the2500and3500mg/kg body weight that included agitation, abnormal movements and hyperactivity. These changes continued for 30min were followed by fatigue, anorexia, and mice became located at one corner of the cageAbortions occurred at the rates15% and40%following the doses 2500 and 3500mg/kg body weight, respectively. This was coupled with the occurrence of 34%,65% and 80% doses of malformation due to the doses 1500,3500and3500mg/kg body weight respectively. Malformations included mongolism, stunted growth, head defects (encephalomeningocele and circular head which appeared as bird head), displacement of eyes and ears, skin wrinkling and flabness, skeletal deformities, and aberrations of limbs and tail.&#x0D; Pathological lesions were developed on the fetuses included hypercellularity of the cerebral cortex ,edema of the meninges and ophthalmic changes delayed growth and development of many parts of the eye, damage of the lens, edema of the outer plexiform layers of the retina and duplication of the retina. These results supported the putative pathological effect of glue smoke in brain and eyes of pregnant mice and their embryos.

Investigating Unexpected Shortening of Height of A Middle-Aged Woman: A Case Report

Osteitis fibrosa cystica (OFC) is a late sequela of untreated hyperparathyroidism caused by the autonomous secretion of parathyroid hormone (PTH). It is characterized by bone pain, skeletal deformities, and pathological fractures. OFC is caused by hypersecretion of PTH, leading to demineralization of bone and pathological fractures. We report a case of unusual presentation of OFC in a middle aged woman who noticed gradual shortening of her height within a particular period of time. Apart from height reduction, the patient had weight loss and pain in different parts of the body for over a decade. Despite being treated with analgesics and steroids initially, there was no significant improvement in her condition. Treatment history included surgical reduction of right elbow fracture and empirical anti-tubercular drug twice as there was a suspicion of disseminated tuberculosis. The patient developed lytic changes, skeletal deformities, and osteoporosis, and was diagnosed with a solitary parathyroid adenoma on the right side. Bangladesh J. Nuclear Med. 26(1): 58-61, 2023

Dissecting the Complexity of Skeletal-Malocclusion-Associated Phenotypes: Mouse for the Rescue.

Skeletal deformities and malocclusions being heterogeneous traits, affect populations worldwide, resulting in compromised esthetics and function and reduced quality of life. Skeletal Class III prevalence is the least common of all angle malocclusion classes, with a frequency of 7.2%, while Class II prevalence is approximately 27% on average, varying in different countries and between ethnic groups. Orthodontic malocclusions and skeletal deformities have multiple etiologies, often affected and underlined by environmental, genetic and social aspects. Here, we have conducted a comprehensive search throughout the published data until the time of writing this review for already reported quantitative trait loci (QTL) and genes associated with the development of skeletal deformation-associated phenotypes in different mouse models. Our search has found 72 significant QTL associated with the size of the mandible, the character, shape, centroid size and facial shape in mouse models. We propose that using the collaborative cross (CC), a highly diverse mouse reference genetic population, may offer a novel venue for identifying genetic factors as a cause for skeletal deformations, which may help to better understand Class III malocclusion-associated phenotype development in mice, which can be subsequently translated to humans. We suggest that by performing a genome-wide association study (GWAS), an epigenetics-wide association study (EWAS), RNAseq analysis, integrating GWAS and expression quantitative trait loci (eQTL), micro and small RNA, and long noncoding RNA analysis in tissues associated with skeletal deformation and Class III malocclusion characterization/phenotypes, including mandibular basic bone, gum, and jaw, in the CC mouse population, we expect to better identify genetic factors and better understand the development of this disease.

Minerals and Glucose Among Patients With Vitamin (D) Deficiency

According to previous studies, vitamin D deficiency might increase the risk of mineral deficiency, and type 2 diabetes mellitus. The aim of this study was to evaluate the level of calcium, phosphorus, calcium to phosphorus ratio, magnesium, and fasting blood glucose in blood serum of patients with vitamin D deficiency. This case-control study comprised 71 patients, 30 subjects sufficient in vitamin D classified as control group (Mean value of vitamin D was 30.67. ± 5.94 ng/dl), and 41 patients suffering from vitamin D deficiency, and insufficiency chosen as the case group (Mean value of vitamin D was 9.79 ± 3.12 ng/dl) .There was lower significant difference in the level of calcium (Ca), calcium–to-phosphorus ratio (Ca/P), and magnesium (Mg) in cases compared to control, but there was higher significant difference in the level of phosphorus (P), and fasting blood glucose (FBG) in cases compared to controls. Serum vitamin D levels showed significantly positive correlations with Ca, and Ca/P ratio, and negative correlation with P. However, vitamin D demonstrated insignificant positive correlation with Mg, and insignificant negative correlation with FBG. The study concluded that, vitamin D deficiency associated with diabetes risk, in addition to mineral deficiency, which associated with various disorders, such as skeletal deformities, osteoporosis, Osteomalacia, cardiovascular diseases, and metabolic syndrome.

Clinical Manifestation of Nebulin-Associated Nemaline Myopathy.

Nemaline myopathy (NM) is a genetically heterogeneous inherited myopathy related with at least 12 genes, whereas pathogenic variants in NEB gene are the most common genetic cause. The clinical spectrum of NM caused by NEB pathogenic variants (NM-NEB) is very broad, ranging from mild to severe presentations manifesting with generalized weakness, as well as respiratory and bulbar involvement. There is currently not enough data regarding the progression of the disease. In this study, we present a genotypic and phenotypic spectrum of 33 patients with NM caused by NEB variants (NM-NEB) classified according to age groups and the use of ventilatory support. We focused on interventional support, genotype-phenotype correlation, and association between respiratory, bulbar, and motor systems in groups of patients stratified by age and by the use of ventilatory support (VS). Clinical and genetic data from patients with NM-NEB followed up in one specialized center were collected through regular consultations. Patients were evaluated regarding motor, bulbar, and respiratory functions. Thirty-three patients with NM-NEB were evaluated consisting of 15 females and 18 males with an average age of 18 (±12) years and a median of 17 (±11) years. 32% of patients with NM-NEB used a G tube, 35% were not able to walk without support, and 55% needed VS. Scoliosis and dysphagia were more common among patients who used VS. Described for the first time, half of the patients presented tongue atrophy in a triple furrow pattern, and the presence of the atrophy was associated with dysphagia. Comparing the patients grouped by age, we found that, proportionally, older patients had more scoliosis and respiratory dysfunction than younger groups, suggesting the progression of the disease in these domains. In addition to that, we showed that VS use was associated with scoliosis and dysphagia. NM-NEB is a very debilitating disease. There is an association between scoliosis and respiratory dysfunction while patients using VS have more often scoliosis than the no-VS group. Triple furrow tongue atrophy is a novel and frequent finding, which is directly associated with dysphagia. Grouping patients by age suggested disease stability in motor and swallow function, but a progression in respiratory dysfunction and skeletal deformities. All observations are relevant in the management care of patients with NM.

Disabling hearing loss after Lefort I osteotomies in patients with history of Eustachian tube dysfunction: An unknown complication

IntroductionThe aim of this study was to determine the predisposing factors of this deafness after orthognathic surgery for a population with no history of cleft palate. Material and methodsAll patients with significant auditory symptoms after orthognathic surgery performed in the department of Craniomaxillofacial surgery in the Croix Rousse Hospital, Lyon, France, since 2012 were included in the study. The exclusion criterion was a history of cleft palate. Bone movements performed during orthognathic surgery were analyzed. An audiometric assessment, including Pure Tone Audiometry and tympanometry, was performed at day 30 (D30), day 60 (D60) and day 90 (D90). ResultsSix patients were included in the study. All patients were women with a mean age of 33.5 years and suffered from class III skeletal deformities. The average hearing loss was 40 dB at D30, 20 dB at D60 and 5 dB at D90 with sometimes differences between the two ears. Five patients had a type C tympanogram suggesting Eustachian tube dysfunction and one patient had a type B tympanogram. All patients benefited from maxillary advancement of 5 mm on average. DiscussionThis study allows to conclude that female patients with a history of allergy or catarrhal tubal deafness are at risk of deafness after orthognathic surgery. These patients must be informed of this complication before surgery and be reassured about its reversibility.

A Novel Approach in the Development of Larval Largemouth Bass Micropterus salmoides Diets Using Largemouth Bass Muscle Hydrolysates as the Protein Source.

This study's objectives were to determine the effect of Largemouth Bass (LMB) muscle hydrolysates obtained using same-species digestive enzymes and the degree of LMB muscle hydrolysis when included in the first feeds of growth performance and survival, skeletal development, intestinal peptide uptake, and muscle-free amino acid composition of larval LMB. LMB muscle was mixed with digestive enzymes from adult LMB, and hydrolyzed for 1.5, 3, and 6 h, respectively. Five diets were produced, the intact diet containing non-hydrolyzed muscle and four diets with 37% muscle hydrolysate inclusion. Those diets were characterized by their level of each hydrolysate (presented as a ratio of 1.5, 3, and 6 Ts hydrolysates): 1:1:1, 1:3:6, 1:3:1, 6:3:1 for diets A, B, C, and D, respectively. To account for gut development, one group of larval LMB was fed a weekly series of diets B, C, and D to provide an increasing molecular weight profile throughout development. This group was compared against others that received either; (1) diets D, C, and B; (2) diet A; or (3) intact diet. The initial inclusion of the hydrolysates significantly improved the total length of the larval LMB; however, neither the hydrolysate inclusion nor the series of dietary molecular weight profiles improved the overall growth of larval LMB. The inclusion of hydrolysates significantly decreased the occurrence of skeletal deformities. The degree of hydrolysis did not have a significant effect on the parameters measured, except for intestinal peptide uptake, which was increased in the group that received the most hydrolyzed diet at the final time of sampling. The lack of overall growth improvement suggests that while the hydrolysates improve the initial growth performance, further research is necessary to determine the optimal molecular weight profile, hydrolysate inclusion level, and physical properties of feeds for larval LMB.