Diagnosis of musculoskeletal abnormalities based on improved lightweight network for multiple model fusion.

This paper introduces a solution to address the intricacy of the model employed in the deep learning-based diagnosis of musculoskeletal abnormalities and the limitations observed in the performance of a single deep learning network model. The proposed approach involves the integration of an improved EfficientNet-B2 model with MobileNetV2, resulting in the creation of FusionNet. First, EfficientNet-B2 is combined with coordinate attention (CA) to obtain CA-EfficientNet-B2. Furthermore, aiming to minimize the model parameter count, we further enhanced the mobile inverted residual bottleneck convolution module (MBConv) employed for feature extraction in EfficientNet-B2, resulting in the development of CA-MBC-EfficientNet-B2. Next, the features extracted from CA-MBC-EfficientNet-B2 and MobileNetV2 are fused. Finally, the final diagnosis of musculoskeletal abnormalities was performed by using fully connected layers. The experimental results demonstrate that, first, compared to EfficientNet-B2, CA-MBC-EfficientNet-B2 not only significantly improves the diagnostic performance of musculoskeletal abnormalities, it also reduces the parameter count and storage space by 17%. Moreover, as compared to other models, FusionNet demonstrates remarkable performance in the area of anomaly diagnosis, particularly on the elbow dataset, achieving a precision of 92.93%, an AUC of 93.89% and an accuracy of 87.10%.

Facilitating the Molecular Diagnosis of Rare Genetic Disorders Through Facial Phenotypic Scores.

With recent advances in computer vision, many applications based on artificial intelligence have been developed to facilitate the diagnosis of rare genetic disorders through the analysis of patients' two-dimensional frontal images. Some of these have been implemented on online platforms with user-friendly interfaces and provide facial analysis services, such as Face2Gene. However, users cannot run the facial analysis processes in house because the training data and the trained models are unavailable. This article therefore provides an introduction, designed for users with programming backgrounds, to the use of the open-source GestaltMatcher approach to run facial analysis in their local environment. The Basic Protocol provides detailed instructions for applying for access to the trained models and then performing facial analysis to obtain a prediction score for each of the 595 genes in the GestaltMatcher Database. The prediction results can then be used to narrow down the search space of disease-causing mutations or further connect with a variant-prioritization pipeline. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Using the open-source GestaltMatcher approach to perform facial analysis.

Combined Repair of Upper Sternal Cleft and Pectus Excavatum in a Child.

Sternal cleft accompanied by pectus excavatum is a rare type of congenital anomaly of the chest wall. Surgical correction is a suitable approach to restore the heart, large vessels, and respiratory dynamics early. This is a report of the successful surgical correction of upper sternal cleft anomaly accompanied by pectus excavatum in a child. The pectus excavatum was corrected without the use of any prosthesis. The cleft was closed by primary approximation with enough dissected pectoralis major muscle and partial thymectomy, mobility, and flexibility ensured by pectus correction. The integrity of the sternum and the chest wall was normal at the end of the 12-month follow-up period.

Expanding the phenotype of PIK3C2A related syndrome: Report of two siblings with novel features and genotype.

A pair of siblings was ascertained due to multiple congenital anomalies, including strikingly similar facial, skeletal, and ocular abnormalities. Exome sequencing of both the children and their mother revealed two novel PIK3C2A variants in the siblings, c.4381delC (p.Arg1461Glufs*31) and c.1555C > T (p.Arg519Ter). PIK3C2A belongs to the Class IIa family of Phosphatidylinositol-3-kinases, which create second messenger lipids that regulate a wide range of downstream signaling pathways involved in cell growth, survival and migration. Tiosano et al. (2019) identified the first monogenic disorder associated with biallelic PIK3C2A loss-of-function variants (oculoskeletodental syndrome). The novel syndrome was characterized by short stature, coarse facial features, ocular and skeletal abnormalities. This report describes two additional siblings affected by the PIK3C2A-related syndrome, confirms core clinical features, establishes intrafamilial variability and expands the phenotype to include proteinuria.

Proteus Syndrome: Case Report with Anatomopathological Correlation.

Background: Proteus syndrome is characterized by a progressive segmental or patchy growth of bone, skin, adipose tissue, and central nervous system, associated with a wide range of neoplasms, pulmonary pathology, and thrombotic risk. The main histological findings are diffuse patchy overgrowth of skin and subcutaneous tissue, plantar cerebriform connective tissue nevus, and ossification defects. Case report: We present a patient that met the clinical and histological criteria necessary for the diagnosis of the disease. He required multiple surgical interventions, including amputation of the right foot. Genetic evaluation confirmed an AKT1 mutation. Discussion: CLOVES syndrome, neurofibromatosis 1 or PTEN hamartoma tumor syndrome are partially superimposable entities to Proteus syndrome and may generate diagnostic doubt. Although the clinical criteria and histologic findings are indicative, the diagnostic confirmation of this entity is genetic.

Loss of Wnt16 Leads to Skeletal Deformities and Downregulation of Bone Developmental Pathway in Zebrafish.

Wingless-type MMTV integration site family, member 16 (wnt16), is a wnt ligand that participates in the regulation of vertebrate skeletal development. Studies have shown that wnt16 can regulate bone metabolism, but its molecular mechanism remains largely undefined. We obtained the wnt16-/- zebrafish model using the CRISPR-Cas9-mediated gene knockout screen with 11 bp deletion in wnt16, which led to the premature termination of amino acid translation and significantly reduced wnt16 expression, thus obtaining the wnt16-/- zebrafish model. The expression of wnt16 in bone-related parts was detected via in situ hybridization. The head, spine, and tail exhibited significant deformities, and the bone mineral density and trabecular bone decreased in wnt16-/- using light microscopy and micro-CT analysis. RNA sequencing was performed to explore the differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the down-regulated DEGs are mainly concentrated in mTOR, FoxO, and VEGF pathways. Protein-protein interaction (PPI) network analysis was performed with the detected DEGs. Eight down-regulated DEGs including akt1, bnip4, ptena, vegfaa, twsg1b, prkab1a, prkab1b, and pla2g4f.2 were validated by qRT-PCR and the results were consistent with the RNA-seq data. Overall, our work provides key insights into the influence of wnt16 gene on skeletal development.

CLOVES Syndrome Diagnosis and Treatment in an Adult Patient.

CLOVES syndrome is a rare, nonheritable sporadic overgrowth disorder. In the world 130-200 cases have been reported. This is the first case of CLOVES described in Portugal, which had been not been diagnosed for the last 36 years. With this paper, the authors look to highlight the clinical features of this syndrome so that it does not go unrecognized in daily practice. The authors also underline the efficacy and safety of sirolimus, and that this treatment should not be denied, even in adult patients.

An adult Chinese patient with developmental delay with short stature, dysmorphic features, and sparse hair (Loucks-Innes syndrome).

Variants of the diphthamide biosynthesis I (DPH1, OMIM*603527) are associated with developmental delay, short stature, and sparse hair syndrome (DEDSSH/DPH1 syndrome) (OMIM# 616901). Another name is Loucks-Innes syndrome. DPH1 syndrome is an ultrarare and severe neurodevelopmental disorder. Less than 20 patients were reported from different ethnicities. Here, we described the first Chinese adult with genetically confirmed DPH1 syndrome. We summarized previously reported patients in the literature and found that developmental delay, unusual skull shape, sparse hair, and facial dysmorphism were consistently present in all DPH1 syndrome patients. Dysplastic toenails and dental abnormalities are age-dependent characteristics of DPH1 syndrome. Our patient was the first reported patient with documented growth hormone deficiency. Dental and endocrine checkup should be considered in the routine follow-up of DPH1 syndrome patients.

Reconstruction of the Mediastinum and Tracheopexy for Tracheomalacia in Straight Back Syndrome.

Tracheomalacia in straight back syndrome results from chronic compression of the trachea and the mainstem bronchi mainly because of decreased mediastinal diameter. The mainstay of correction is the increase of mediastinal space and the restoration of the tracheal lumen and stability. Owing to the great variability of the manifestation of this disease, individualized approaches are required. We describe our approach in a 36-year-old woman with straight back syndrome associated severe tracheobronchomalacia with reconstruction of the proximal aorta, brachiocephalic artery, sternoplasty, and anterior tracheopexy, which resulted in successful treatment of the condition.

Bilateral bipartite lunate misdiagnosed as carpal fracture: a case report and brief review of literature.

Bilateral bipartite lunate is a very rare congenital anomaly of the lunate. A 36-year-old military European male was referred to our service diagnosed with a lunate fracture. Symptoms began 3 months before our encounter, after falling on his outstretched left hand. The patient was misdiagnosed with a lunate fracture, therefore treated with a cast and then transitioned to a removable splint over 2 months in total; When the patient presented to our facility, on physical examination, he referred pain over the dorso-ulnar side of the wrist, especially the ulnar snuff. Tenderness to palpation over the fovea and positive triangular fibrocartilage complex axial compression test was encountered. Bilateral wrist X-rays were taken, and a diagnosis of bilateral bipartite lunate was made by our team. The patient was treated for ulnar-sided wrist pain with steroid injection and physical rehabilitation. A literature review on bipartite lunate was conducted, and cases share three basic common features: unilateral involvement, incidentally diagnosed after a traumatic event, and absence of positive clinical findings related to the bipartition.

Musculoskeletal abnormalities in a large international cohort of boys with 49,XXXXY.

49,XXXXY is the rarest X and Y chromosomal variation, with an incidence of 1 in 80,000-100,000 live male births and has been associated with numerous musculoskeletal abnormalities. Data was collected from an international cohort of boys with 49,XXXXY over 10 years. Children were evaluated by a multidisciplinary team consisting of a pediatric orthopedist, a neurogeneticist, a neurodevelopmentalist, and two physical therapists. Increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67.6%), pes planus (65.2%), and other foot abnormalities (86.9%) were observed. Several anomalies increased with age, specifically hamstring tightness, kyphosis, and scoliosis. The elucidation of the orthopedic profile of this population is necessary in order to provide healthcare providers with current medical information. This research further supports the necessity for the comprehensive multidisciplinary treatment of boys with 49,XXXXY.

Determination of congenital absence of palmaris longus tendon with clinical examination and ultrasonography.

OBJECTIVES: The tendon of the palmaris longus is commonly used as a tendon graft in many reconstructive surgeries. Palmaris longus absence (PLA) was found in 15% among individuals worldwide. In this prospective study, we aimed to conduct an incidence study in which physical examination methods were confirmed by ultrasonography in PLA, and to evaluate the relationship of absence with age, gender, laterality and dominant hand. METHODS: The study included 490 cases. They were initially tested to evaluated by physical examination using the Schaeffer's and Hiz-Ediz test for the assessment of the palmaris longus tendon. Additional ultrasonography was performed to confirm its absence in 129 wrists of 78 cases whose tendons could not be visualized or palpated. RESULTS: The incidence of tendon absence was 13% by physical examination methods. According to the final results when we added ultrasonography to physical examination methods, the incidence of unilateral, bilateral and overall absence of the palmaris longus were 5%, 9% and 11% respectively. There was no statistically significant difference between individuals with and without PLA in terms of gender, side, age and dominant hand (p = 0.796, p = 0.622, p = 0.397 and p = 0.187, respectively). However, bilateral PLA was statistically significantly higher than unilateral in both genders (p = 0.011). CONCLUSIONS: We think that agenesis should be proven accurately by ultrasonographic examination for the final result before any surgical procedure with palmaris longus tendon. Furthermore measuring the diameter of the palmaris longus tendon by preoperative ultrasonography can be useful for surgeons who plan a procedure that requires specific measurements.

Molecular analysis of a uterine broad ligament leiomyoma in a patient with CLOVES syndrome.

Overgrowth syndromes are characterized by a global or regional excess growth of various tissue types, especially of mesenchymal nature. The CLOVES (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined-type Vascular malformations, Epidermal naevi, Scoliosis/Skeletal and spinal anomalies) syndrome is characterized by an asymmetric growth excess associated with PIK3CA mutations, found in mosaic, affecting the lesional, but not the normal tissues. Herein, we report the case of a patient affected by CLOVES syndrome, harboring a 13 cm leiomyoma of the uterine broad ligament. The leiomyoma tissue was examined by next-generation sequencing showing the absence of related mutations.

Orthopedic issues in vascular anomalies.

Vascular anomalies impact the musculoskeletal system dependent on the tissue involved (skin, subcutis, muscle, cartilage, or bone), the extent of involvement, and the type of anomalous vessels (arteries, capillaries, veins, or lymphatics). These malformations can cause a multitude of musculoskeletal problems for the patient. Leg-length discrepancy, intra-articular involvement, muscular lesions, and primary or secondary scoliosis are amongst the issues that patients face. All of these problems can cause pain, deformity, and a range of functional limitations. Surgical and nonsurgical treatment plans have a role in patient care. Patients with vascular anomalies may also suffer from life-threatening cardiovascular and hematologic abnormalities. For those patients who undergo surgery, the thromboembolic risk is elevated, wound breakdown and infection are much more common, and bleeding risk continues well into the postoperative course. Because of the complex nature of these disorders, the clinician must have a full understanding of the types of lesions, their natural history, appropriate diagnostic studies, associated medical problems, indications for treatment, and treatment options. For severe malformations, especially syndromes such as CLOVES and Klippel- Trenaunay syndrome, interdisciplinary team management is essential for the best outcomes.

De Novo and Inherited Variants in GBF1 are Associated with Axonal Neuropathy Caused by Golgi Fragmentation.

Distal hereditary motor neuropathies (HMNs) and axonal Charcot-Marie-Tooth neuropathy (CMT2) are clinically and genetically heterogeneous diseases characterized primarily by motor neuron degeneration and distal weakness. The genetic cause for about half of the individuals affected by HMN/CMT2 remains unknown. Here, we report the identification of pathogenic variants in GBF1 (Golgi brefeldin A-resistant guanine nucleotide exchange factor 1) in four unrelated families with individuals affected by sporadic or dominant HMN/CMT2. Genomic sequencing analyses in seven affected individuals uncovered four distinct heterozygous GBF1 variants, two of which occurred de novo. Other known HMN/CMT2-implicated genes were excluded. Affected individuals show HMN/CMT2 with slowly progressive distal muscle weakness and musculoskeletal deformities. Electrophysiological studies confirmed axonal damage with chronic neurogenic changes. Three individuals had additional distal sensory loss. GBF1 encodes a guanine-nucleotide exchange factor that facilitates the activation of members of the ARF (ADP-ribosylation factor) family of small GTPases. GBF1 is mainly involved in the formation of coatomer protein complex (COPI) vesicles, maintenance and function of the Golgi apparatus, and mitochondria migration and positioning. We demonstrate that GBF1 is present in mouse spinal cord and muscle tissues and is particularly abundant in neuropathologically relevant sites, such as the motor neuron and the growth cone. Consistent with the described role of GBF1 in Golgi function and maintenance, we observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals in this study. Our results not only reinforce the existing link between Golgi fragmentation and neurodegeneration but also demonstrate that pathogenic variants in GBF1 are associated with HMN/CMT2.

Recurrent c.776T>C mutation in CHST3 with four other novel mutations and a literature review.

The chondrodysplasia with congenital joint dislocations, CHST3 type, which was distinguished by predominantly contractures, marked vertebral changes, and normal facial appearance. Although, some clinical clues can be used for differential diagnosis, it is mostly too difficult to discriminate one type from another on basis of clinical findings only. Eight patients with multiple dislocations from five unrelated families were included in this study to elucidate molecular diagnoses. Clinical exome sequencing (CES) was performed on one patient from each family. Variable degree vertebral changes, pes equinovarus, and kyphoscoliosis accompanied multiple dislocations and short stature. In CES analyses, all mutations showed in CHST3. Previously reported c.776T>C homozygous mutations were detected in two families, compound heterozygous novel c.740G>C and c.881T>C mutations were found in one family, and homozygous novel c.564C>A and c.963G>A mutations were also determined in remaining two families, separately. Biallelic CHST3 c.776T>C mutations are most frequent mutation in CHST3 and have been reported predominantly in Turkish patients which may be remarkable for genotype-ethnicity correlation in chondrodysplasia with congenital joint dislocations, CHST3 type. It is suggested that c.776T>C mutation can be accepted as a recurrent mutation in CHST3 for Turkish patients who are suspected of having chondrodysplasia with congenital joint dislocations, CHST3 type.

A unique case of mid-tendonpalmaris longus muscle - dissection presentation and literature review

The palmaris longus (PL) muscle is one of five muscles that originates from the common flexor tendon, which attaches at the medial epicondyle of the humerus, and has its own insertion distally into the palmar aponeurosis. Although the PL contributes minimal biomechanical function, its wide anatomic variation can produce pathologies in the forearm and wrist such as median nerve entrapment. The present work describes a unique case of a PL distally migrated muscle belly with wide tendon both proximal and distal not noted in other anatomical or surgical reference materials. Here-in, the current case is compared to previously re-ported PL variations and their documented frequencies by region and ethnicity. Key findings include several studies showing Caucasian populations with greater than 25% frequencies of absent PL, compared to 4-6% in African regions. Potential explanations for this finding include evolutionary adaptations associated with manual labor and need for increased grip strength. In addition, the considerations of abnormal PL in surgical procedures inclusive of challenges in graft procedures that might present with such anatomic variations of the PL are examined

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Rare anatomic variation on a 10,000-year-old South American skeleton: the case of Iuzu, Toca dos Coqueiros, Piauí State, Brazil.

PURPOSE: A skeleton named Iuzu has been unearthed from an exceptional middle Holocene burial in Toca dos Coqueiros site, in Serra da Capivara National Park (UNESCO World Heritage Site, Piauí State, Brazil). During a bioarchaeological analysis of its remains, we discovered that Iuzu was suffering from rare vertebral malformations. A double foramen transversaria, the agenesis of a foramen on the atlas and the hypoplasia of the transverse process of the axis have been highlighted. We aimed to deduce the clinical consequences of the malformation on the patient's health. METHODS: We proceeded to macroscopic observation and radiography of the bones, then we search for other examples of such a pathology in archaeological litterature. RESULT: The malformation caused vascular insufficiency that may have led to neurological lesions leading to various pains and troubles. The very rare malformations Iuzu presented have not been found on a paleoindian skeleton from South America so far. CONCLUSION: This case allowed us to examine the conditions of selection of individuals buried in southern Piauí during the Middle Holocene, during which time this rite does not seem to predominate.