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While it is widely thought that de novo mutations (DNMs) occur randomly, we previously showed that some DNMs are enriched because they are positively selected in the testes of aging men. These "selfish" mutations cause disorders with a shared presentation of features, including exclusive paternal origin, significant increase of the father's age, and high apparent germline mutation rate. To date, all known selfish mutations cluster within the components of the RTK-RAS-MAPK signaling pathway, a critical modulator of testicular homeostasis. Here, we demonstrate the selfish nature of the SMAD4 DNMs causing Myhre syndrome (MYHRS). By analyzing 16 informative trios, we show that MYHRS-causing DNMs originated on the paternally derived allele in all cases. We document a statistically significant epidemiological paternal age effect of 6.3 years excess for fathers of MYHRS probands. We developed an ultra-sensitive assay to quantify spontaneous MYHRS-causing SMAD4 variants in sperm and show that pathogenic variants at codon 500 are found at elevated level in sperm of most men and exhibit a strong positive correlation with donor's age, indicative of a high apparent germline mutation rate. Finally, we performed in vitro assays to validate the peculiar functional behavior of the clonally selected DNMs and explored the basis of the pathophysiology of the different SMAD4 sperm-enriched variants. Taken together, these data provide compelling evidence that SMAD4, a gene operating outside the canonical RAS-MAPK signaling pathway, is associated with selfish spermatogonial selection and raises the possibility that other genes/pathways are under positive selection in the aging human testis.

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Bruck syndrome is an autosomal recessive form of osteogenesis imperfecta caused by biallelic variants in PLOD2 or FKBP10 and is characterized by joint contractures, bone fragility, short stature, and scoliosis. PLOD2 encodes LH2, which hydroxylates type I collagen telopeptide lysines, a critical step for collagen crosslinking. The Plod2 global knockout mouse model is limited by early embryonic lethality, and thus, the role of PLOD2 in skeletogenesis is not well understood. We generated a novel Plod2 mouse line modeling a variant identified in two unrelated individuals with Bruck syndrome: PLOD2 c.1559dupC, predicting a frameshift and loss of the long isoform LH2b. In the mouse, the duplication led to loss of LH2b mRNA as well as significantly reduced total LH2 protein. This model, Plod2fs/fs, survived up to E18.5 although in non-Mendelian genotype frequencies. The homozygous frameshift model recapitulated the joint contractures seen in Bruck syndrome and had indications of absent type I collagen telopeptide lysine hydroxylation in bone. Genetically labeling tendons with Scleraxis-GFP in Plod2fs/fs mice revealed the loss of extensor tendons in the forelimb by E18.5, and developmental studies showed extensor tendons developed through E14.5 but were absent starting at E16.5. Second harmonic generation showed abnormal tendon type I collagen fiber organization, suggesting structurally abnormal tendons. Characterization of the skeleton by µCT and Raman spectroscopy showed normal bone mineralization levels. This work highlights the importance of properly crosslinked type I collagen in tendon and bone, providing a promising new mouse model to further our understanding of Bruck syndrome.

Bruck syndrome is a rare disease where individuals have brittle bone as well as contracted or stiff joints. Mutations in two genes are associated with Bruck syndrome and, in this work, we focus on PLOD2. Mice without Plod2 die at an early embryonic stage, before they have a chance to fully develop. In this work, we created a mouse with a PLOD2 mutation seen in people with Bruck syndrome. Some of these new Bruck syndrome model mice survived to a later gestational age, but all died at birth. The Bruck syndrome mice were small and had contracted joints. We found that they were missing tendons in their arms and had structurally abnormal tendons in their knees. Bone mineralization was normal, but there were indications that the modifications needed for normal type I collagen structure were absent. Overall, this is an advantageous new mouse model of Bruck syndrome that can be used to study this rare disease and highlights the importance of Plod2 in tendon.

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Burns of the hand are prevalent and must be managed aggressively in the acute phase to prevent deformity and disability. Proper early wound management, achieving durable soft tissue coverage, and appropriate positioning in the acute period offer substantial benefits to patients long-term. When contractures occur, secondary procedures are often indicated, and they range from laser therapy to local/regional flap coverage; rarely free flaps are used. Boutonniere deformities are common, and unfortunately, at times finger amputation renders the hand more functional than further efforts at reconstruction.

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A 19-year-old girl presented with symmetric and bilateral hyperpigmentation, an indurated lesion that initially appeared on the axillary fold at the age of 14, which then extended to the lower back, anterior aspect of both thighs, and popliteal fold. No hypertrichosis was observed (Figure 1).The patient was the youngest of the four children, born from the first-degree consanguineous marriage. She was born at full term and weighed 2,420 g at birth. No similar patient was present in the family. The patient experienced delayed motor acquisition and stature growth (3rd percentile) until the age of 4. Right hypoacusis was diagnosed at the age of 6. She developed hallux valgus, flexion contracture of the fin-gers and toes, barrel deformity of the anterior thorax, and recurrent fever. The laboratory tests, including fasting blood glucose, -triglycerides, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were normal. Her abdominal, pelvic, and transthoracic ultrasound scans were normal, with no hepatosplenomegaly, lymphadenopathy, or cardiac abnormalities. Histologic analysis demonstrated patchy acanthosis of the epidermis, with orthokeratotic hyperkeratosis. Keratinocyte hyperpigmentation and spongiosis at certain areas were observed with moder-ate inflammation because of the infiltration of lymphocytes, histiocytes, and plasma cells. Immunohistochemical analysis showed macrosialin (CD68+) and common gamma chain (γc) CD132. Germline mutations in the SLC29A3 gene were not analyzed. The patient was prescribed dermocorticoids with depigmentation therapy, which demonstrated moderate clinical evolution.

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In order to clarify the pathways closely linked to denervated muscle contracture, this work uses IoMT-enabled healthcare stratergies to examine changes in gene expression patterns inside atrophic muscles following brachial plexus damage. The gene expression Omnibus (GEO) database searching was used to locate the dataset GSE137606, which is connected to brachial plexus injuries. Strict criteria (|logFC|≥2 & adj.p < 0.05) were used to extract differentially expressed genes (DEGs). To identify dysregulated activities and pathways in denervated muscles, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were used. Hub genes were found using Cytoscape software's algorithms, which took into account parameters like as proximity, degree, and MNC. Their expression, enriched pathways, and correlations were then examined. The results showed that 316 DEGs were predominantly concentrated in muscle-related processes such as tissue formation and contraction pathways. Of these, 297 DEGs were highly expressed in denervated muscles, whereas 19 DEGs were weakly expressed. GSEA showed improvements in the contraction of striated and skeletal muscles. In addition, it was shown that in denervated muscles, Myod1, Myog, Myh7, Myl2, Tnnt2, and Tnni1 were elevated hub genes with enriched pathways such adrenergic signaling and tight junction. These results point to possible therapeutic targets for denervated muscular contracture, including Myod1, Myog, Myh7, Myl2, Tnnt2, and Tnni1. This highlights treatment options for this ailment which enhances the mental state of patient.

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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. CONCLUSION: 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.

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BACKGROUND: When the range of motion between two finger segments, both active and passive, is restricted, finger contracture occurs. The aim of this study is to investigate the best procedure to eliminate finger contracture and the functional and esthetic results of the different surgical procedures. MATERIALS AND METHODS: A total of 31 patients with soft-tissue abnormalities of the hand were included in this prospective study. They underwent either contracture removal with K-wire and skin grafts or various flap procedures in the department of plastic surgery. Complaints of stiffness and discomfort were classified into five categories: none, mild, moderate, marked, and severe. The difficulty a person had in picking up objects, grasping, writing, etc., was used to determine the degree of disability. Absenteeism from work and surgical site infections were also recorded. RESULTS: The mean age was 20.25 years, with a mean age of 23.05 for men and 15.83 for women. Overall, most cases occurred in the age range of 3-10 years. For K-wire surgery with skin grafting, the typical time off work was 24 days. The average recovery time ranged from 15.2 days for skin grafts to 16.9 days for tenolysis, 28.33 days for groyne flaps, and 41 days for abdominal flaps. Of all cases, 12 (38.00%) had a fair result, 10 (31.04%) had a moderate result, and 9 (30.96%) had an excellent result. CONCLUSION: The most feasible method for treating these situations, which offers the greatest potential for a functional and cosmetic result, is contracture reduction with skin grafting.

Résumé Contexte:Lorsque l'amplitude de mouvement entre deux segments de doigts, actifs et passifs, est restreinte, une contracture des doigts se produit. Le Le but de cette étude est d'étudier la meilleure procédure pour éliminer la contracture des doigts et les résultats fonctionnels et esthétiques des différents interventions chirurgicales.Matériels et méthodes:Au total, 31 patients présentant des anomalies des tissus mous de la main ont été inclus dans cette étude prospective. étude. Ils ont subi soit une ablation des contractures avec du fil K et des greffes de peau, soit diverses procédures de lambeau dans le service de chirurgie plastique. Les plaintes de raideur et d'inconfort ont été classées en cinq catégories: aucune, légère, modérée, marquée et grave. La difficulté d'une personne qu'ils avaient à ramasser des objets, à les saisir, à écrire, etc., a été utilisé pour déterminer le degré d'incapacité. Absentéisme au travail et sur le site chirurgical des infections ont également été enregistrées.Résultats:L'âge moyen était de 20,25 ans, avec un âge moyen de 23,05 ans pour les hommes et de 15,83 ans pour les femmes. Dans l'ensemble, la plupart des cas sont survenus dans la tranche d'âge de 3 à 10 ans. Pour la chirurgie au fil K avec greffe de peau, le temps d'arrêt typique était de 24 jours. La moyenne le temps de récupération variait de 15,2 jours pour les greffes de peau à 16,9 jours pour la ténolyse, 28,33 jours pour les lambeaux d'épi et 41 jours pour les lambeaux abdominaux. Parmi tous les cas, 12 (38,00 %) ont eu un résultat passable, 10 (31,04 %) ont eu un résultat modéré et 9 (30,96 %) ont eu un excellent résultat.Conclusion:le plus La méthode réalisable pour traiter ces situations, qui offre le plus grand potentiel de résultat fonctionnel et esthétique, est la réduction des contractures. avec greffe de peau.

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OBJECTIVE: To establish a predictive scoring model for bladder neck contracture (BNC) after laparoscopic enucleation of the prostate with preservation of the urethra (Madigan surgery) and explore the preventive measures against this postoperative complication. METHODS: We included 362 cases of BPH treated by laparoscopic Madigan surgery from January 2019 to March 2022 (45 with and 317 without postoperative BNC) in the training group and another 120 cases treated the same way in the verification group, collected the clinical data on the patients and evaluated the results of surgery. Using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression, we analyzed the risk factors for postoperative BNC and constructed a predictive scoring model for evaluation of the factors. RESULTS: Compared with the baseline, the IPSS, quality of life (QOL) score and postvoid residual urine volume (PVR) were significantly decreased (P < 0.05) while the maximum urinary flow rate (Qmax) remarkably increased (P < 0.05) in the BPH patients at 3 months after surgery. Eight non-zero characteristic predictors were identified by LASSO regression analysis. Multivariate logistic regression analysis showed that short clinical experience of the surgeon, concurrent prostatitis, bladder rinse solution temperature <34℃, catheter blockage, urethral balloon injection volume >40 ml and postoperative constipation were independent risk factors for postoperative BNC (P < 0.05). The best cut-off value was 2.36 points in both the training and the verification groups. The results of evaluation exhibited a high discriminability of the predictive scoring model. CONCLUSION: Laparoscopic Madigan surgery is a safe and effective method for the treatment of BPH. Short clinical experience of the surgeon, concurrent prostatitis, bladder rinse solution temperature <34℃, catheter blockage, water injected into the urethral balloon >40 ml and postoperative constipation were independent risk factors for postoperative BNC. The predictive scoring model constructed in this study has a good discriminability and is simple and feasible, contributive to the prediction of postoperative BNC in BPH patients undergoing laparoscopic Madigan surgery.

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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.

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BACKGROUND: This study investigates the association between additional distal femoral resection and improved flexion contracture in total knee arthroplasty (TKA) with a robot-assisted system. Flexion contracture is a common issue in patients with knee osteoarthritis, which causes postoperative complications and functional limitations. This study aims to evaluate the effectiveness of additional bone resection in flexion contracture correction and knee extension angle improvement after the actual surgical steps. METHODS: The study included 11 patients who underwent posterior-stabilized (PS)-type TKA with a robot-assisted system. The surgical technique consisted of precise bone resection and range of motion evaluation using a navigation system. A precut technique was used to facilitate posterior access and remove osteophytes that cause the contracture. The amount of additional distal femoral resection was determined based on the thickness of the insert trial required for achieving full extension. RESULTS: The flexion contracture correction angle and the amount of additional distal femoral resection demonstrated a linear relationship. An average of 2.0° with the standard error (SE) of 0.6° improvement in flexion contracture was observed per 1.0 mm of additional bone resection. The postoperative evaluation demonstrated a significant improvement in knee extension angle, thereby reducing the contracture degree. CONCLUSION: This study was the first to perform the additional distal femoral resection on the living knee, which closely replicates the actual surgical steps. The current study revealed that an additional 1.0 mm of distal femoral resection in PS-type TKA improves knee extension angle by 2.0° (SE 0.6°) within an additional resection range of 1.0 mm to 3.3 mm.

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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.

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INTRODUCTION: severe, rigid hip abduction deformity in individuals with cerebral palsy (CP) is an exceptionally uncommon condition. This posture hinders the positioning in the wheelchair and the completion of basic activities of daily living (ADL). Addressing such severe deformities can be quite challenging. MATERIAL AND METHODS: a 14-year-old male, with spastic-dystonic quadriplegic CP, developed rigid and severe flexion-abduction contractures in both hips, characterized by 90 degrees of flexion and 100 degrees of abduction. These contractures severely impeded his ability to comfortably use a wheelchair and even pass through doorways. Performing basic ADLs became a significant challenge for both the patient and his caregivers. RESULTS: the treatment approach involved a two-stage surgical procedure, one for each hip, with a two-month interval between them. An extensive release of the fascia latae, gluteus maximus, external rotators, and hip flexors; in combination with a proximal femur osteotomy were performed. To maintain the corrections achieved, long-leg casts connected with two bars were employed, followed by orthotic support and physiotherapy. Following the procedure, lower limb adduction was achieved, and the patient and caregivers were highly satisfied, as ADLs and basic caregiving had been greatly facilitated. CONCLUSIONS: while the available literature on the management of severe rigid abduction hip contractures in non-ambulatory CP patients is limited, and treatment options are often complex, the present case underscores the effectiveness of a comprehensive approach involving soft tissue release and bone surgery. Achieving a more favorable wheelchair positioning and facilitating basic ADLs and care represents a significant success for patients and families.

INTRODUCCIÓN: la deformidad severa y rígida en abducción de cadera en individuos con parálisis cerebral (PC) es una condición infrecuente. Esta postura dificulta el posicionamiento en la silla de ruedas y la realización de actividades básicas de la vida diaria (AVD). El tratamiento de estas deformidades tan severas puede ser todo un reto. MATERIAL Y MÉTODOS: varón de 14 años, con PC tetrapléjica espástica-distónica, que desarrolló contracturas rígidas y severas de flexión-abducción en ambas caderas, caracterizadas por 90 grados de flexión y 100 grados de abducción. Estas contracturas impedían gravemente su capacidad para utilizar cómodamente una silla de ruedas e incluso pasar por las puertas. La realización de actividades básicas de la vida diaria se convirtió en un reto importante tanto para el paciente como para sus cuidadores. RESULTADOS: el tratamiento consistió en una intervención quirúrgica en dos fases, una para cada cadera, con un intervalo de dos meses entre ellas. Se realizó una amplia liberación de la fascia lata, el glúteo mayor, los rotadores externos y los flexores de la cadera; en combinación con una osteotomía proximal del fémur. Para mantener las correcciones conseguidas, se emplearon escayolas de pierna larga conectadas con dos barras, seguidas de soporte ortésico y fisioterapia. Tras la intervención, se consiguió la aducción de los miembros inferiores y el paciente y los cuidadores se mostraron muy satisfechos, ya que se habían facilitado en gran medida las AVD y los cuidados básicos. CONCLUSIONES: aunque la bibliografía disponible sobre el tratamiento de las contracturas rígidas graves de la cadera en abducción en pacientes no deambulantes con PC es limitada, y las opciones de tratamiento suelen ser complejas, el presente caso subraya la eficacia de un enfoque integral que incluye la liberación de los tejidos blandos y la cirugía ósea. Conseguir una posición más favorable en la silla de ruedas y facilitar las AVD básicas y los cuidados representa un éxito significativo para los pacientes y sus familias.

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BACKGROUND: Stiff skin syndrome (SSS) is a rare disease characterized by thickened, indurated skin and limited joint movement. Multiple diverse phenotypes have been reported, and the correlation of severity with the clinical heterogeneity and histopathological findings of SSS needs to be refined. OBJECTIVE: To define subtypes based on clinical features and predict the prognosis of a new SSS classification. METHODS: Eighty-three patients with SSS were retrospectively reviewed for clinicopathological manifestations and routine laboratory workup, including 59 cases obtained from a PubMed search between 1971 and 2022 and 24 cases diagnosed in our department between 2003 and 2022. RESULTS: Among the 83 patients, 27.7, 41, and 31.3% had classic widespread, generalized segmental, and localized SSS, respectively. Joint immobility was present in 100, 71, and 20% of classic, generalized, and localized cases, respectively. Histopathologic findings were common among the 3 groups, and based on that, we further found a difference in the distribution of proliferative collagen. 54.5% of classic and 50% of generalized cases occurred throughout the dermis or the subcutis, whereas 76% of localized cases were mainly involved in the reticular dermis or subcutis. In patients with incipient localized SSS, 42% (21/50) developed generalized SSS, and only 6% (3/50) progressed to classic SSS, whereas more than half of the incipient generalized SSS cases (60.6%, 20/33) developed classic SSS. LIMITATIONS: This retrospective study was limited to previously published cases with limited data. CONCLUSIONS: We propose a distinct clinical classification characterized by lesion distribution, including classic widespread, generalized segmental, and localized SSS, associated with disease severity and prognosis.

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BACKGROUND: Axillary cicatricial contracture is a debilitating condition that can greatly impair shoulder joint function. Therefore, timely correction of this condition is imperative. In light of Ogawa's prior classification of axillary cicatricial contracture deformities, we have proposed a novel classification system and reconstruction principles based on a decade of treatment experience. Our proposed system offers a more comprehensive approach to correcting axillary cicatricial contracture deformities and aims to improve patient outcomes. METHODS: Our study included 196 patients with a total of 223 axillary cicatricial contracture deformities. The range of shoulder abduction varied between 10 and 120 degrees. Our treatment approach included various methods such as the lateral thoracic flap, transverse scapular artery flap, cervical superficial artery flap, medial upper arm flap, latissimus dorsi flap, Z-shape modification, and the use of local flaps combined with skin grafting. After 2 weeks, the sutures were removed, and patients were instructed to start functional exercises. To categorize the deformities, we divided them into 2 types: axillary-adjacent region cicatricial contracture (type I) and extended area contracture (type II). RESULTS: For each subtype, a specific treatment method was chosen based on a designed algorithm decision tree. Out of the total cases, 133 patients underwent treatment with various types of local flaps, including Z-plasty, whereas 63 patients received treatment involving skin grafting and different types of local flaps. At the time of discharge, the abduction angle of the shoulder joint ranged from 80 to 120 degrees. Among the 131 patients who were followed up, 108 of them adhered to a regimen of horizontal bar exercises. After a 1-year follow-up period, the abduction angle of the shoulder joint had significantly improved to a range of 110-180 degrees. CONCLUSIONS: We have proposed a novel classification method for the correction of axillary cicatricial contracture deformity. This approach involves utilizing distinct correction strategies, in conjunction with postoperative functional exercise, to ensure the effectiveness of axillary reconstruction.

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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.

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Objective: To examine the feasibility and clinical effect of all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture. Methods: This is a retrospective case series study. From February 2021 to February 2023, the clinical data of 24 patients (30 feet) with Achilles tendon contracture treated with all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening were analyzed retrospectively. There were 10 males and 14 females, aged (32.8±16.1) years (range: 9 to 62 years). There were 8 cases of left side only, 10 cases of right side only and 6 cases of bilateral. There were 14 cases (16 feet) of foot varus, 4 cases (6 feet) of foot valgus, and 6 cases (8 feet) without deformity. All patients underwent all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening. The surgical effects were evaluated using the maximum dorsal extension angle of ankle joint in knee extension position, the visual analogue scale (VAS) of pain, the American Orthopedic Foot and Ankle Society ankle-hindfoot score(AOFAS-AH). Paired sample t test was used to compare the scores before and after operation. Results: All patients successfully completed the operation, and the operation time of Achilles tendon lengthening was (22.0±5.7)minutes (range: 15 to 35 minutes) and the intraoperative blood loss was (6.5±2.7)ml (range: 2 to 15 ml). All patients primarily healing without any complications such as sural nerve injury, Achilles tendon rupture, important blood vessel injury, and obvious decrease of lift heel strength of achilles tendon. All 24 patients were followed up for (17.2±4.5) months (range: 12 to 28 months). One patient suffered from lift heel's weakness in one foot after operation, and recovered after repeated lift heel functional exercises. The ankle dorsiflexion function of two patients with calf triceps spasm were not improved after operation, and it was obviously improved after botulinum toxin injection. At the last follow-up, the maximum dorsal extension angle of ankle joint in knee extension position increased from -9.2°±7.6°(range:-25° to 5°) preoperatively to 14.5°±7.0°(range:0° to 28°)(t=24.83, P<0.01); the VAS score was reduced from (4.5±1.7) points (range:1 to 8 points) preoperatively to (1.5±0.9) points (range:0 to 3 points) (t=9.53, P<0.01), the AOFAS-AH was increased from (60.5±11.4)points (range:38 to 85 points) to (90.8±5.4) points (range:80-100 points)(t=14.21, P<0.01). Conclusions: All-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture not only provides Achilles tendon lengthening, but also avoids complications such as Achilles tendon rupture and sural nerve injury. It is an effective method for the treatment of Achilles tendon contracture.

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PURPOSE: This report presents the results of using cryopreserved umbilical amniotic membrane (cUAM) as an alternative mucosal graft for ocular surface reconstruction in cases of anophthalmic socket contracture (ASC), cicatricial entropion (CE), and conjunctival-scleral defects. METHODS: The study included patients who underwent non-commercial implantation of cUAM grafts (prepared by corneal banking methods) for ASC, CE, conjunctival defect, and scleral melting. The main success criteria for this study were the comfortable fitting of the ocular prosthesis in ASC patients, the natural eyelid position in CE patients, and the degree of conjunctivalisation in melting patients. RESULTS: cUAM transplantation was performed in 2 patients who could not use a prosthetic eye due to conjunctival contracture, 2 patients with CE, and 1 patient with conjunctival defect and 1 patient with conjunctival-scleral melting. The primary outcome was achieved in 83.3% (5/6) of patients. In one patient with CE, partial healing was achieved due to the persistence of CE in the medial upper eyelid. CONCLUSIONS: cUAM is a viable alternative to mucosal grafting for reconstructing the bulbar and palpebral conjunctival surface, fornix, and orbit, with reduced donor morbidity and shorter surgical time. Its regenerative ability allows for tissue defect healing and improves cosmetic appearance through epithelialization within weeks.

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ABSTRACT: Congenital flexion contracture of ulnar digits is a rare entity with few cases reported in medical literature. This condition is often misdiagnosed as Volkmann ischemic contracture as both have similar presentation. The patient history, physical examination, radiological investigation, and intra-operative findings can differentiate these 2 conditions clearly. A 14-year-old female presented to a tertiary care hospital with flexion deformity of the left long, ring, and little fingers without neurological deficit since she was 3 years old. Patient had decreased handspan with difficulty in grasping daily life objects. Finger flexion deformity was also not aesthetically acceptable due to social stigma. Patient finger contracture was managed with flexor pronator slide (Max-Page) operation. The muscle slide operation was done using concealed medial incision. Aesthetic and functional correction was achieved with no recurrence at subsequent follow-ups.

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