RESUMEN
BACKGROUND: SMAD6 encodes an intracellular inhibitor of the bone morphogenetic protein (BMP) signalling pathway. Until now, rare heterozygous loss-of-function variants in SMAD6 were demonstrated to increase the risk of disparate clinical disorders including cardiovascular disease, craniosynostosis and radioulnar synostosis. Only two unrelated patients harbouring biallelic SMAD6 variants presenting a complex cardiovascular phenotype and facial dysmorphism have been described. CASES: Here, we present the first two patients with craniosynostosis harbouring homozygous SMAD6 variants. The male probands, both born to healthy consanguineous parents, were diagnosed with metopic synostosis and bilateral or unilateral radioulnar synostosis. Additionally, one proband had global developmental delay. Echocardiographic evaluation did not reveal cardiac or outflow tract abnormalities. MOLECULAR ANALYSES: The novel missense (c.[584T>G];[584T>G], p.[(Val195Gly)];[(Val195Gly)]) and missense/splice-site variant (c.[817G>A];[817G>A], r.[(817g>a,817delins[a;817+2_817+228])];[(817g>a,817delins[a;817+2_817+228])], p.[(Glu273Lys,Glu273Serfs*72)];[(Glu273Lys,Glu273Serfs*72)]) both locate in the functional MH1 domain of the protein and have not been reported in gnomAD database. Functional analyses of the variants showed reduced inhibition of BMP signalling or abnormal splicing, respectively, consistent with a hypomorphic mechanism of action. CONCLUSION: Our data expand the spectrum of variants and phenotypic spectrum associated with homozygous variants of SMAD6 to include craniosynostosis.
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Craneosinostosis , Radio (Anatomía)/anomalías , Sinostosis , Cúbito/anomalías , Humanos , Masculino , Craneosinostosis/diagnóstico , Craneosinostosis/genética , Radio (Anatomía)/metabolismo , Cúbito/metabolismo , Mutación Missense/genética , Proteína smad6/genética , Proteína smad6/metabolismoRESUMEN
Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) type 2, caused by MDS1 and EVI1 complex locus (MECOM) gene mutations, is a rare inherited bone marrow failure syndrome (IBMFS) with skeletal anomalies, characterized by varying presentation of congenital thrombocytopenia (progressing to pancytopenia), bilateral proximal radioulnar synostosis, and other skeletal abnormalities. Due to limited knowledge and heterogenous manifestations, clinical diagnosis of the disease is challenging. Here we reported a novel MECOM mutation in a Chinese boy with typical clinical features for RUSAT-2. Trio-based whole exome sequencing of buccal swab revealed a novel heterozygous missense mutation in exon 11 of the MECOM gene (chr3:168818673; NM_001105078.3:c.2285G > A). The results strongly suggest that the variant was a germline mutation and disease-causing mutation. The patient received matched unrelated donor hematopoetic stem cell transplantation (HSCT). This finding was not only expanded the pathogenic mutation spectrum of MECOM gene, but also provided key information for clinical diagnosis and treatment of RUSAT-2.
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Mutación Missense , Radio (Anatomía) , Sinostosis , Trombocitopenia , Cúbito , Humanos , Masculino , China , Proteína del Locus del Complejo MDS1 y EV11/genética , Mutación , Radio (Anatomía)/anomalías , Trombocitopenia/genética , Trombocitopenia/diagnóstico , Factores de Transcripción/genética , Cúbito/anomalíasRESUMEN
OBJECTIVE: To evaluate the effect of an induced synostosis with a screw on pronation and supination in cats. STUDY DESIGN: Ex vivo biomechanical study. SAMPLE POPULATION: A total of 58 feline forelimbs. METHODS: A total of 58 cadaveric feline thoracic limbs were mounted on a custom-built jig with the elbow and carpus flexed at a 90° angle. To exclude any orthopedic disease, radiographs of the forelimbs were performed prior to the mechanical tests. Radioulnar synostosis was imitated with a 2 mm cortical screw through the radius into the ulna in the proximal (Group P; n = 54), middle (Group M; n = 52), and distal (Group D; n = 53) radial diaphysis. The angles of pronation and supination were recorded after manually applying a two-finger tight rotational force to the metacarpus. Rotational tests were performed without a screw (Group N) and with a screw in each of the aforementioned positions. Pairwise comparisons between the groups were performed based on their angles of rotation with a paired t-test with the Benjamini-Hochberg procedure and a mixed model ANOVA. RESULTS: Mean angles of rotation decreased between Group N (129.5 ± 15.9°) and all groups with imitated radioulnar synostosis to a mean angle of 37.5 ± 14.5° (p < .0001). Mean angles of rotation did not differ between the groups with imitated radioulnar synostosis. CONCLUSION: Induced radioulnar synostosis decreases antebrachial rotation by more than two-thirds, regardless of location. CLINICAL SIGNIFICANCE: Implants fixating the radius to the ulna should be avoided in cats, regardless where they are located along the radial diaphysis.
Asunto(s)
Enfermedades de los Gatos , Radio (Anatomía)/anomalías , Sinostosis , Cúbito/anomalías , Gatos , Animales , Radio (Anatomía)/cirugía , Pronación , Supinación , Cúbito/cirugía , Sinostosis/cirugía , Sinostosis/veterinaria , CadáverRESUMEN
We report a fetus with hydrops, congenital heart disease and bilateral radioulnar synostosis caused by a novel pathogenic MECOM variant. The female fetus was referred for post-mortem examination after fetal hydrops and intrauterine death was diagnosed at 20 weeks gestation. Post-mortem examination confirmed fetal hydrops, pallor, truncus arteriosus and bilateral radioulnar synostosis. Trio whole genome sequencing analysis detected a novel de novo heterozygous pathogenic loss-of-function variant in MECOM (NM_004991), associated with a diagnosis of Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia 2 (RUSAT-2). RUSAT-2 is a variable condition associated postnatally with bone marrow failure, radioulnar synostosis and congenital anomalies. RUSAT-2 is not currently associated with a prenatal phenotype or fetal demise, and was not present on diagnostic NHS prenatal gene panels at time of diagnosis. This case highlights the diagnostic value of detailed phenotyping with post-mortem examination, and of using a broad sequencing approach.
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Hidropesía Fetal , Sinostosis , Femenino , Humanos , Embarazo , Hidropesía Fetal/diagnóstico , Hidropesía Fetal/genética , Proteína del Locus del Complejo MDS1 y EV11 , Diagnóstico Prenatal , Radio (Anatomía)/anomalías , Sinostosis/complicaciones , Sinostosis/genética , Cúbito/anomalíasRESUMEN
Background and Objectives: Proximal radioulnar synostosis (PRUS) is the most frequent congenital forearm disorder, although the prevalence in the general population is rare with a few hundred cases reported. Pfeiffer, Poland, Holt-Oram, and other serious congenital syndromes contain this abnormality. Non-syndromic cases with isolated PRUS very often exhibit as SMAD6, NOG genes variants, or sex chromosome aneuploidy. A subgroup of patients with haematological abnormalities presents with HOXA11 or MECOM genes variants. Case report: We present a non-syndromic adult elite ice-hockey player with unilateral proximal radioulnar synostosis of the left forearm. In early childhood he was able to handle the hockey stick only as a right-handed player and the diagnosis was set later at the age of 8 years due to lack of supination. Cleary-Omer Type III PRUS was found on x-ray with radial head hypoplasia and mild osteophytic degenerative changes of humeroulnar joint. Since the condition had minimal impact on sports activities, surgical intervention was not considered. The player continued his ice-hockey career at the top level and joined a national team for top tournaments. Upper extremity function assessment with questionnaires and physical testing resulted in minimal impairment. The most compromised tool was the Failla score with 10 points from a total of 15. Genetic testing with Sanger sequencing revealed no significant pathogenic variant in SMAD6, NOG, and GDP5 genes. No potentially pathogenic copy number variants were detected by array-based comparative genomic hybridization. Conclusions: In the reported case, the ability of an athlete to deal with an anatomic variant limiting the forearm supination is demonstrated. Nowadays, a comprehensive approach to rule out more complex musculoskeletal impairment and family burden is made possible by evolving genetics.
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Radio (Anatomía) , Cúbito , Masculino , Adulto , Humanos , Preescolar , Niño , Hibridación Genómica Comparativa , Radio (Anatomía)/anomalías , Radio (Anatomía)/cirugía , Cúbito/anomalías , Cúbito/cirugía , AtletasRESUMEN
PURPOSE: Publications evaluating the results of the ulna lengthening in congenital radial deficiency are based only on small groups of subjects which yield statistical studies of low scientific value. The aim was to examine the effectiveness of ulna lengthening in radial longitudinal deficiency and determine the number and quality of complications based on one of the most numerous study groups described in the literature. METHODS: The material consists of a study group with 31 upper limbs of unmatured patients diagnosed with type III and IV radial longitudinal deficiency. The study group was evaluated based on the parameters known from the literature. The difficulties during elongation were classified according to Paley's classification. RESULTS: The study group contained patients with a mean age of 9 years, and the number of boys and girls was comparable. Ulna length significantly increased after elongation compared to the initial bone length. The patient's age didn't affect the ulna lengthening, and the amount of elongation didn't significantly affect the total stabilization period. However, the total stabilization time increased with increasing patient age. Difficulties affected more than half of the cases. CONCLUSIONS: Ulna elongation in congenital radial deficiency results in significant lengthening of the ulna, and thus the entire forearm, compared to the initial bone length. This technique has a high percentage of difficulty, so its use should be considered after cautious discussion with the parents and patients.
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Alargamiento Óseo , Osteogénesis por Distracción , Masculino , Femenino , Humanos , Niño , Osteogénesis por Distracción/métodos , Cúbito/cirugía , Cúbito/anomalías , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/cirugía , Radio (Anatomía)/anomalías , Antebrazo , Alargamiento Óseo/métodosRESUMEN
PURPOSE: The etiology for a considerable proportion of patients with congenital radioulnar synostosis (RUS) remains unclear. This study aimed to investigate the genetic cause of RUS without a known cause. METHODS: Patients with RUS were investigated. Exome sequencing and/or Sanger sequencing was performed. Bioinformatics analysis was also performed. Pathogenicity was evaluated for variants of interest. RESULTS: We identified unique missense variants in MECOM (encodes EVI1) associated with RUS in 8 families. Of them, 6 families had variants in residue R781, including 3 families with R781C (c.2341C>T), 2 families with R781H (c.2342G>A), and 1 family with R781L (c.2342G>T). Another 2 variants included I783T (c.2348T>C) in 1 family and Q777E (c.2329C>G) in 1 family. All these variants were clustered within the ninth zinc finger motif of EVI1. Phenotype evaluation identified that most of these patients with RUS harboring mutant MECOM had finger malformations, but none of them had identifiable hematological abnormalities. Functional experiments showed that MECOM R781C led to alterations in TGF-ß-mediated transcriptional responses. CONCLUSION: This study examined MECOM variants by focusing on RUS instead of hematological abnormalities. The R781 residue in EVI1 is a hotspot for human RUS variants. Mutant MECOM is the second most common cause for familial RUS.
Asunto(s)
Sinostosis , Humanos , Proteína del Locus del Complejo MDS1 y EV11/genética , Linaje , Radio (Anatomía)/anomalías , Sinostosis/genética , Factores de Transcripción/genética , Cúbito/anomalíasRESUMEN
Bi-allelic variants in COLEC11 and MASP1 have been associated with 3MC syndrome, a clinical entity made of up four rare autosomal recessive disorders: Carnevale, Mingarelli, Malpuech, and Michels syndromes, characterized by variable expression of facial dysmorphia, cleft lip/palate, postnatal growth deficiency, hearing loss, cognitive impairment, craniosynostosis, radioulnar synostosis, and genital and vesicorenal anomalies. More recently, bi-allelic variants in COLEC10 have been described to be associated with 3MC syndrome. Syndromic features seen in 3MC syndrome are thought to be due to disruption of the chemoattractant properties that influence neural crest cell migration. We identified nine individuals from five families of Ashkenazi Jewish descent with homozygosity of the c.311G > T (p.Gly104Val) variant in COLEC10 and phenotype consistent with 3MC syndrome. Carrier frequency was calculated among 52,278 individuals of Jewish descent. Testing revealed 400 carriers out of 39,750 individuals of Ashkenazi Jewish descent, giving a carrier frequency of 1 in 99 or 1.01%. Molecular protein modeling suggested that the p.Gly104Val substitution alters local conformation. The c.311G > T (p.Gly104Val) variant likely represents a founder variant, and homozygosity is associated with features of 3MC syndrome. 3MC syndrome should be in the differential diagnosis for individuals with short stature, radioulnar synostosis, cleft lip and cleft palate.
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Anomalías Múltiples , Labio Leporino , Fisura del Paladar , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Labio Leporino/diagnóstico , Labio Leporino/genética , Fisura del Paladar/diagnóstico , Fisura del Paladar/genética , Colectinas/genética , Humanos , Judíos/genética , Mutación , Fenotipo , Radio (Anatomía)/anomalías , Sinostosis , Cúbito/anomalíasRESUMEN
BACKGROUND: The development of radioulnar synostosis due to post-traumatic injuries of the elbow or forearm can lead to debilitating outcomes. Several treatment options are available to hinder the progression and prevent recurrence. We used a combination of these treatments in a series of patients and observed the outcomes. METHODS: We conducted a retrospective study of 10 patients with post-traumatic radioulnar synostosis (9 men and 1 woman) who required surgical intervention in a tertiary orthopedic center. All of these patients were subjected to the same treatment combination (preoperative radiotherapy, tissue interposition after heterotopic ossification resection, and adjuvant indomethacin postoperatively). Improvement in range of motion (flexion, extension, and rotation) and the Mayo score was assessed and compared preoperatively and postoperatively via statistical analysis. RESULTS: In comparison to the patients' preoperative state, which ranged from poor to fair, all 10 patients reported excellent Mayo scores after intervention with the triple therapy combination, with a mean Mayo score of 36 ± 10.2 points. Flexion, extension, and rotation improved by mean values of 55.2° ± 38.7°, 50.2° ± 34.0°, and 47.9° ± 40.0°, respectively. There was 1 complication that has subsided on follow-up. CONCLUSION: The triple therapy combination was found to provide good functional and prophylactic results preventing recurrence.
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Articulación del Codo , Sinostosis , Articulación del Codo/cirugía , Femenino , Humanos , Kuwait , Masculino , Radio (Anatomía)/anomalías , Rango del Movimiento Articular , Estudios Retrospectivos , Sinostosis/etiología , Sinostosis/cirugía , Resultado del Tratamiento , Cúbito/anomalíasRESUMEN
BACKGROUND: Many operative methods have been reported for the treatment of congenital radioulnar synostosis (CRUS) and their indications remain controversial. The aim of this study is to evaluate the clinical, radiologic, and functional results of the 2-stage derotational osteotomy with periosteal preservation for CRUS in children. METHODS: From a total of 102 children with CRUS, a retrospective evaluation of 14 consecutive patients (18 forearms) who underwent 2-stage derotational osteotomy of the distal third radius and proximal third ulna with periosteal preservation, bone segment removal, morselization and grafting and cast immobilization was performed. Children with bilateral involvement and/or pronation (>60 degrees), and substantial functional limitations in daily activities were considered candidates for surgery to obtain the desired position of 0 to 20 degrees of pronation. Electronic medical records, preoperative and postoperative clinical and radiologic examinations were reviewed. Also, functional results and parental satisfaction were assessed and statistically analyzed. RESULTS: The median age at the time of surgery was 6.87 (5.02 to 11.22) years. The median follow-up was 38.62 (24.79 to 81.20) months. The median preoperative pronation deformity was 80 (70 to 90) degrees, while the final position was 0 (0 to 10) degrees of pronation ( P <0.01). Elbow flexion and extension showed no changes after surgery. All patients successfully achieved union at 8 (6 to 10) weeks. No complications were observed, and no patient required revision surgeries. The ability to perform daily activities improved markedly, and all patients were satisfied with the results of the surgery. CONCLUSIONS: Two-stage double-level intraperiosteal derotational osteotomy is a safe, simple, and effective procedure in children with CRUS with severe deformity and limitation in performing basic daily living activities. Functional improvement and patient satisfaction are total, and so far no complications have been reported. LEVEL OF EVIDENCE: Level III-treatment study, retrospective comparative study.
Asunto(s)
Sinostosis , Niño , Humanos , Osteotomía/métodos , Radio (Anatomía)/anomalías , Estudios Retrospectivos , Sinostosis/cirugía , Cúbito/anomalías , Cúbito/cirugíaRESUMEN
Retinoic acid exposures as well as defects in the retinoic acid-degrading enzyme CYP26B1 have teratogenic effects on both limb and craniofacial skeleton. An initial report of four individuals described a syndrome of fetal and infantile lethality with craniosynostosis and skeletal anomalies caused by homozygous pathogenic missense variants in CYP26B1. In contrast, a 22-year-old female was reported with a homozygous missense pathogenic variant in CYP26B1 with complex multisuture craniosynostosis and intellectual disability, suggesting that in some cases, biallelic pathogenic variants of CYP26B1 may be compatible with life. Here we describe four additional living individuals from two families with compound heterozygous pathogenic missense variants in CYP26B1. Structural assessment of these additional missense variants places them further from the catalytic site and supports a model consistent with milder nonlethal disease. In addition to previously reported findings of multisuture craniosynostosis, conductive hearing loss, joint contractures, long slender fingers, camptodactly, broad fingertips, and developmental delay/intellectual disability, skeletal imaging in our cases also revealed gracile long bones, gracile ribs, radioulnar synostosis, and carpal and/or tarsal fusions. These individuals broaden the phenotypic range of biallelic pathogenic variants in CYPB26B1 and most significantly clarify that mortality can range from perinatal lethality to survival into adulthood.
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Anomalías Múltiples/patología , Homocigoto , Mutación Missense , Radio (Anatomía)/anomalías , Ácido Retinoico 4-Hidroxilasa/genética , Sinostosis/patología , Cúbito/anomalías , Anomalías Múltiples/genética , Niño , Familia , Femenino , Humanos , Lactante , Masculino , Fenotipo , Radio (Anatomía)/patología , Sinostosis/genética , Cúbito/patologíaRESUMEN
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.
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Cromosomas Humanos X/genética , Síndrome de Klinefelter/diagnóstico , Anomalías Musculoesqueléticas/diagnóstico , Enfermedades Raras/diagnóstico , Adolescente , Niño , Preescolar , Cromosomas Humanos Y , Pie Plano/complicaciones , Pie Plano/diagnóstico , Pie Plano/genética , Pie Plano/fisiopatología , Tendones Isquiotibiales/diagnóstico por imagen , Tendones Isquiotibiales/fisiopatología , Humanos , Lactante , Síndrome de Klinefelter/complicaciones , Síndrome de Klinefelter/genética , Síndrome de Klinefelter/fisiopatología , Cifosis/complicaciones , Cifosis/diagnóstico , Cifosis/genética , Cifosis/fisiopatología , Masculino , Anomalías Musculoesqueléticas/complicaciones , Anomalías Musculoesqueléticas/genética , Anomalías Musculoesqueléticas/fisiopatología , Radio (Anatomía)/anomalías , Radio (Anatomía)/fisiopatología , Enfermedades Raras/complicaciones , Enfermedades Raras/genética , Enfermedades Raras/fisiopatología , Escoliosis/complicaciones , Escoliosis/diagnóstico , Escoliosis/genética , Escoliosis/fisiopatología , Sinostosis/complicaciones , Sinostosis/diagnóstico , Sinostosis/genética , Sinostosis/fisiopatología , Tortícolis/complicaciones , Tortícolis/diagnóstico , Tortícolis/genética , Tortícolis/fisiopatología , Cúbito/anomalías , Cúbito/fisiopatologíaRESUMEN
PURPOSE: To investigate whether computer-aided design (CAD) and 3-dimensional printing technology can assist in accurate completion of ulna-radius proximal rotational osteotomy in congenital radioulnar synostosis (CRUS). METHODS: We treated 1 right arm and 4 left arms of 4 boys with a mean age of 5.2 years (range, 4.3-6.0 years) between July 2018 and April 2019. Computed tomography (CT) scans of the forearm were performed on the children before surgery. Using the CT data, the pronation angle of the forearm was measured. An individualized dial with a matching forearm diameter was designed before surgery to control the angle of the rotational osteotomy. Ulna and radius models, and individualized dials, were prepared for each patient using 3-dimensional printing technology. Preoperative simulated surgery was performed using the 3-dimensional printed models. During the surgery, 2 Kirschner wires were used as operating levers for rotation, and rotational angle correction was precisely controlled using the dial. The cast and internal fixation were removed after x-ray examination showed that the osteotomy had healed, about 5 weeks after surgery. RESULTS: The rotational osteotomies were completed in a single operation, and the correction angle was 60°. No complications occurred after the operation. All patients showed functional improvements in activities of daily living. CONCLUSIONS: For CRUS patients, models and dials made with CAD and 3-dimensional printing technology can assist in precise rotational osteotomy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.
Asunto(s)
Actividades Cotidianas , Sinostosis , Niño , Preescolar , Humanos , Masculino , Osteotomía , Impresión Tridimensional , Radio (Anatomía)/anomalías , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/cirugía , Sinostosis/diagnóstico por imagen , Sinostosis/cirugía , Tecnología , Cúbito/anomalías , Cúbito/diagnóstico por imagen , Cúbito/cirugíaRESUMEN
INTRODUCTION: Congenital proximal radioulnar synostosis (CPRUS) is a relatively rare forearm deformity that is characterized by a fixed pronated forearm of varying severity. The osseous synostosis between the proximal part of the ulna and the radius can be seen on the X-ray images in most cases. Many researchers have attempted to identify methods to measure the disease severity to guide in the treatment of CPRUS. However, to describe the overall deformity, the use of multiple indicators is essential, and some of these measurements require special software or need to be conducted on cadavers. OBJECTIVE: The aim of the current study was to introduce the radius pronation angle (RPA), a novel radiological evaluation index of CPRUS, and analyze the relationship between the RPA and the severity of the deformity. METHODS: Three-dimensional models of 43 CPRUS forearms (19 left forearms and 24 right forearms) of 32 patients (23 males and 9 females; average age was 6 years 8 months; range, from 1.5 to 27 years) treated at Beijing Ji Shui Tan Hospital during 2016 to 2019 were reconstructed using a computer-assisted technique. The special flexed posterior-anterior views of the X-ray image (the f-PA view) of the forearms were obtained, and the forearm rotation angle and the ulnar inner rotation angle were measured on each forearm. The RPA was measured on the f-PA view, and the lengths of the osseous synostosis, ulna, and the radial head were measured on the computed tomography scan images using the multiplanar reconstruction function. The Pearson index was analyzed between the RPA and the other measurements. RESULTS: The RPAs were correlated with the forearm rotation angle, ulnar inner rotation angle, relative length of the osseous synostosis, and the relative length of the radial head (P < 0.05). CONCLUSIONS: The RPA can be measured quickly and easily on the f-PA view of the X-ray image and can be used as a reliable indicator of the severity of CPRUS.
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Radio (Anatomía) , Sinostosis , Preescolar , Femenino , Antebrazo/diagnóstico por imagen , Humanos , Lactante , Masculino , Pronación , Radio (Anatomía)/anomalías , Radio (Anatomía)/diagnóstico por imagen , Sinostosis/diagnóstico por imagen , Cúbito/anomalías , Cúbito/diagnóstico por imagenRESUMEN
BACKGROUND: Post-traumatic proximal radioulnar synostosis is a very rare and disabling condition whose surgical treatment has traditionally been viewed with pessimism. The results of the few case series in the literature are conflicting. Our aims were (1) to describe the clinical results of a case series treated surgically by a single elbow surgeon and (2) to review the literature. METHODS: Twelve patients were evaluated. Preoperative radiographs and computed tomography scans were performed. According to the Viola and Hastings classification, there was 1 case of type IC synostosis; 3, type IIA; 2, type IIIA; and 8, type IIIB. Two patients had a double synostosis. The synostosis was excised in 10 cases; in addition, radial head excision, radial head arthroplasty, and proximal radial diaphyseal resection were performed in 1, 3, and 2 cases, respectively. The Mayo Elbow Performance Score, modified American Shoulder and Elbow Surgeons score, and QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score were used for the preoperative and postoperative evaluation. The nonparametric Wilcoxon signed rank test was used for the statistical analysis. RESULTS: The mean follow-up period was 20.5 months. The final mean extension-flexion and pronation-supination arcs were 116° and 123°, respectively. Significant improvements were found in the Mayo Elbow Performance Score (P = .005), modified American Shoulder and Elbow Surgeons score (P = .012), and QuickDASH score (P = .002), with mean values of 24, 28, and 17, respectively. One synostosis recurrence and one late disassembly of the radial head arthroplasty were observed. CONCLUSIONS: Post-traumatic proximal radioulnar synostosis surgery is effective, but careful preoperative planning based on the pathoanatomic characteristics of each type of synostosis and associated lesions is mandatory. Synostosis excision is performed in most cases, whereas additional surgical procedures should be considered in selected cases.
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Traumatismos del Antebrazo/diagnóstico , Radio (Anatomía)/anomalías , Sinostosis/diagnóstico , Cúbito/anomalías , Adulto , Anciano , Bases de Datos Factuales , Femenino , Traumatismos del Antebrazo/diagnóstico por imagen , Traumatismos del Antebrazo/cirugía , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/cirugía , Rango del Movimiento Articular , Recurrencia , Sinostosis/diagnóstico por imagen , Sinostosis/cirugía , Resultado del Tratamiento , Cúbito/diagnóstico por imagen , Cúbito/cirugíaRESUMEN
PURPOSE: Radioulnar synostosis (RUS) can be syndromic or nonsyndromic. The genetic basis for several RUS syndromes have been reported. However, the genetic cause of nonsyndromic RUS (nsRUS) remains unknown. METHODS: We performed Giemsa (GTG) banding, Sanger sequencing, and exome sequencing on patients (n = 140) and families (n = 11) who suffered from RUS. RESULTS: GTG banding identified 10% RUS sporadic cases affected by sex chromosome aneuploidy. Sanger sequencing on candidate genes revealed noggin (NOG) rarely mutated in nsRUS. Exome sequencing identified 16 loss-of-function (LOF) and 6 missense variants (minor allele frequency [MAF] < 0.0001) in 22/117 nsRUS sporadic patients. Genetic association analysis found a significant association between SMAD6-LOF variants and nsRUS risk (odds ratio [OR] = 430, 95% confidence interval [CI]: 238-780, P < 0.000001). SMAD6 mutated in nsRUS was further confirmed by direct Sanger sequencing of SMAD6-coding regions on other unrelated cohorts of nsRUS cases or families. In summary, we detected 27 SMAD6 rare variants in nsRUS, most of which were LOF variants, 4 were de novo, and 3 were transmitted in families with autosomal dominant inheritance. CONCLUSION: As an intracellular bone morphogenetic protein (BMP) antagonist gene, SMAD6 is frequently mutated in nsRUS. NOG, which encodes an extracellular BMP antagonist, is rarely mutated in nsRUS. This work is the first genetic study on nsRUS.
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Radio (Anatomía)/anomalías , Proteína smad6/genética , Sinostosis/genética , Cúbito/anomalías , Adolescente , Adulto , Alelos , Niño , Preescolar , Familia , Femenino , Frecuencia de los Genes/genética , Humanos , Lactante , Recién Nacido , Masculino , Mutación Missense/genética , Linaje , Penetrancia , Análisis de Secuencia de ADN/métodos , Proteína smad6/metabolismo , Secuenciación del Exoma/métodosRESUMEN
Ulnar hemimelia is a very rare skeletal abnormality characterized by the total or partial absence of the ulna. It is reported to occur in approximately 1 per 150,000 live births. Some shortening of the forearm, radial bowing, and tendency of the hand to drift to the ulnar side of the wrist usually accompany ulnar hemimelia. Other skeletal anomalies such as humeroradial synostosis, radial head dislocation, carpal or metacarpal coalition, and digital abnormalities may also be seen in cases of ulnar hemimelia. The patients may be asymptomatic in the presence of an isolated mild ulnar deficiency. On the other hand, cases of prominent ulnar deficiency accompanied by complex upper limb abnormalities leading to severe disability may also be observed. We herein present four patients with varying degrees of ulnar hemimelia. Our first case had an isolated ulnar hemimelia, whereas the other three had additional upper limb abnormalities of different types.
Asunto(s)
Ectromelia/diagnóstico por imagen , Cúbito/anomalías , Adulto , Diagnóstico Diferencial , Femenino , Humanos , MasculinoRESUMEN
PURPOSE: We evaluated the relationship between the area around the distal radioulnar joint according to the ulnar variances and the cross-sectional area using magnetic resonance imaging (MRI) scans in this prospective study of patients with carpal tunnel syndrome (CTS). METHODS: From among a total of 243 patients who had been diagnosed with CTS between March 2012 and February 2017 at our hospital, 41 patients with positive ulnar variance were enrolled in group 1. As control groups, 39 healthy volunteers who underwent MRI evaluations were included in group 2 (neutral ulnar variance) and group 3 (negative variance). Basic demographic data, including age, sex, and body mass index, were recorded for all 3 groups. An area encompassing the contents of carpal tunnel (nerves/tendons) was designated as area "A," and the area just beneath the subcutaneous fat was designated as area "B" at the levels of the lunate (L) and pisiform (P) on axial MRI. Ratios of these areas ("A/B at L" and "A/B at P") were evaluated in terms of their correlations with ulnar variance. RESULTS: Mean age, sex, and body mass index were not statistically different among the groups, respectively. Within each group, there was no difference between "A/B at L" and "A/B at P," respectively. When comparing the 3 groups, "A/B at L" and "A/B at P" were all significantly decreased in group 1 than in other groups. Regardless of the group, ulnar length negatively correlated with both "A/B at L" and "A/B at P" ratios. CONCLUSIONS: We found a positive relationship between decreased cross-sectional area around the distal radioulnar joint and positive ulnar variance on radiologic investigation. These findings show the importance of variance in the positive ulna variance to the development of CTS.
Asunto(s)
Síndrome del Túnel Carpiano/diagnóstico por imagen , Descompresión Quirúrgica/métodos , Imagen por Resonancia Magnética/métodos , Cúbito/anomalías , Articulación de la Muñeca/diagnóstico por imagen , Adulto , Síndrome del Túnel Carpiano/cirugía , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estudios Prospectivos , Medición de Riesgo , Resultado del Tratamiento , Cúbito/anatomía & histología , Cúbito/diagnóstico por imagen , Articulación de la Muñeca/fisiopatología , Articulación de la Muñeca/cirugíaRESUMEN
Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is an inherited bone marrow failure syndrome, characterized by thrombocytopenia and congenital fusion of the radius and ulna. A heterozygous HOXA11 mutation has been identified in two unrelated families as a cause of RUSAT. However, HOXA11 mutations are absent in a number of individuals with RUSAT, which suggests that other genetic loci contribute to RUSAT. In the current study, we performed whole exome sequencing in an individual with RUSAT and her healthy parents and identified a de novo missense mutation in MECOM, encoding EVI1, in the individual with RUSAT. Subsequent analysis of MECOM in two other individuals with RUSAT revealed two additional missense mutations. These three mutations were clustered within the 8(th) zinc finger motif of the C-terminal zinc finger domain of EVI1. Chromatin immunoprecipitation and qPCR assays of the regions harboring the ETS-like motif that is known as an EVI1 binding site showed a reduction in immunoprecipitated DNA for two EVI1 mutants compared with wild-type EVI1. Furthermore, reporter assays showed that MECOM mutations led to alterations in both AP-1- and TGF-ß-mediated transcriptional responses. These functional assays suggest that transcriptional dysregulation by mutant EVI1 could be associated with the development of RUSAT. We report missense mutations in MECOM resulting in a Mendelian disorder that provide compelling evidence for the critical role of EVI1 in normal hematopoiesis and in the development of forelimbs and fingers in humans.
Asunto(s)
Proteínas de Unión al ADN/genética , Mutación Missense , Proto-Oncogenes/genética , Radio (Anatomía)/anomalías , Radio (Anatomía)/metabolismo , Sinostosis/genética , Trombocitopenia/congénito , Factores de Transcripción/genética , Cúbito/anomalías , Cúbito/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Médula Ósea/anomalías , Médula Ósea/metabolismo , Niño , Preescolar , Exoma , Femenino , Regulación de la Expresión Génica , Hematopoyesis/genética , Humanos , Proteína del Locus del Complejo MDS1 y EV11 , Masculino , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Análisis de Secuencia de ADN , Transducción de Señal , Sinostosis/metabolismo , Trombocitopenia/genética , Trombocitopenia/metabolismo , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Transcripción Genética , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND: Cenani-Lenz Syndactyly (CLS) syndrome is a rare autosomal recessive disorder characterized by syndactyly and oligodactyly of fingers and toes, disorganization and fusion of metacarpals, metatarsals and phalanges, radioulnar synostosis and mesomelic shortness of the limbs, with lower limbs usually being much less affected than upper limbs. CASE PRESENTATION: we report here two patients, born to consanguineous Sri Lankan parents, present with bilateral postaxial oligodactyly limited to upper limbs. While the proband has no noticeable facial dysmorphism, renal impairments or cognitive impairments, his affected sister displays a few mild facial dysmorphic features. Whole exome sequencing of the proband showed a novel deleterious homozygous mutation (c.1348A > G) in the LRP4 gene, resulting in an Ile450-to-Val (I450V) substitution. CONCLUSION: This recessive mutation in LRP4 confirmed the diagnosis of CLS syndrome in two patients present with isolated hand syndactyly. This is the first reported case of CLS syndrome in a family of Sri Lankan origin.