RESUMEN
Dysfunction of a mechanosensor in sensory neurons causes joint contracture.
Asunto(s)
Artrogriposis , Canales Iónicos , Mecanotransducción Celular , Células Receptoras Sensoriales , Humanos , Artrogriposis/genética , Artrogriposis/fisiopatología , Mecanotransducción Celular/genética , Células Receptoras Sensoriales/fisiología , Canales Iónicos/genética , Animales , Ratones , Modelos Animales de EnfermedadRESUMEN
Distal arthrogryposis (DA) is a collection of rare disorders that are characterized by congenital joint contractures. Most DA mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal system. However, gain-of-function mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 (DA5) through unknown mechanisms. We show that expression of a gain-of-function PIEZO2 mutation in proprioceptive sensory neurons that mainly innervate muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects through increased activity within the peripheral nervous system during postnatal development. Furthermore, botulinum toxin (Botox) and a dietary fatty acid that modulates PIEZO2 activity reduce DA5-like deficits. This reveals a role for somatosensory neurons: Excessive mechanosensation within these neurons disrupts musculoskeletal development.
Asunto(s)
Artrogriposis , Contractura , Canales Iónicos , Mecanotransducción Celular , Células Receptoras Sensoriales , Animales , Ratones , Artrogriposis/genética , Artrogriposis/fisiopatología , Contractura/genética , Contractura/fisiopatología , Mecanotransducción Celular/genética , Mutación , Células Receptoras Sensoriales/fisiología , Canales Iónicos/genéticaRESUMEN
RESUMEN La artrogriposis múltiple congénita es una enfermedad de baja frecuencia, esporádica, no progresiva, que aparece en el período prenatal y se caracteriza por varias contracturas articulares presentes al nacimiento en los cuatro miembros. Se estima una incidencia de 1/10 000 nacidos vivos. El diagnóstico es posible al realizar los ultrasonidos en un feto que tiene posiciones viciosas y que no se mueve. La prevalencia de la artrogriposis múltiple congénita es variable, resultando la más frecuente la artrogriposis múltiple clásica (amioplasia), presente entre el 40 y el 50 % de los afectados. La búsqueda ultrasonográfica en el tercer trimestre del embarazo es fundamental con fines diagnósticos, para brindar asesoramiento genético y preparar un equipo para el nacimiento. Es importante tener sospecha diagnóstica para sugerir la vía alta por cesárea, para bienestar fetal. Un grupo multidisciplinario debe llevar a cabo el manejo y tratamiento de estos enfermos. Se presenta el caso de un neonato nacido a las 39 semanas por parto eutócico prolongado por presentación de cara, con sufrimiento fetal agudo, meconio ++++, apgar 5-7, con peso de 3 300 g, que presentó luxación y contractura generalizada de hombros, codos, así como de caderas, rodillas y tobillos, con dedos de manos y pies en flexión.
ABSTRACT Congenital multiple arthrogryposis is a low-frequency, sporadic, non-progressive disease that appears in the prenatal period, and is characterized by several contractures present at birth in the four limbs. The estimated incidence is 1/10 000 born alive. The diagnosis is possible performing ultrasounds on a fetus that has vicious positions and does not move. The prevalence of congenital multiple arthrogryposis is variable, being classical multiple arthrogryposis (amyoplasia) the most frequent one, present in between 40 and 50 % of the affected persons. Ultrasonographic search in the third semester of pregnancy is essential for diagnostic purposes to provide genetic counseling and to prepare a ream for birth. It is important to have diagnostic suspicion to suggest the high cesarean way for fetal well-being. A multidisciplinary group should carry out the management and treatment of these patients. The case of a newborn is presented, who was born at 39 weeks by prolonged eutocic delivery due to presenting face, with acute fetal suffering, meconium ++++, apgar 5-7, weighing 3 300 g, that presented luxation and general contracture of shoulders, elbows, and also hips, knees and ankles, with fingers and toes in flexion.
Asunto(s)
Humanos , Recién Nacido , Artrogriposis/diagnóstico , Artrogriposis/etiología , Artrogriposis/fisiopatología , Pediatría , Artrogriposis/sangre , Artrogriposis/epidemiología , Asesoramiento Genético , Genética Médica , NeurologíaRESUMEN
Spinal muscular atrophy with congenital bone fractures 2 (SMABF2), a type of arthrogryposis multiplex congenita (AMC), is characterized by congenital joint contractures, prenatal fractures of long bones, and respiratory distress and results from biallelic variants in ASCC1. Here, we describe an infant with severe, diffuse hypotonia, congenital contractures, and pulmonary hypoplasia characteristic of SMABF2, with the unique features of cleft palate, small spleen, transverse liver, and pulmonary thromboemboli with chondroid appearance. This infant also had impaired coagulation with diffuse petechiae and ecchymoses which has only been reported in one other infant with AMC. Using trio whole genome sequencing, our proband was identified to have biallelic variants in ASCC1. Using deep next generation sequencing of parental cDNA, we characterized alteration of splicing encoded by the novel, maternally inherited ASCC1 variant (c.297-8 T > G) which provides a mechanism for functional pathogenicity. The paternally inherited ASCC1 variant is a rare nonsense variant (c.466C > T; p.Arg156*) that has been previously identified in one other infant with AMC. This report extends the phenotypic characteristics of ASCC1-associated AMC (SMABF2) and describes a novel intronic variant that partially disrupts RNA splicing.
Asunto(s)
Artrogriposis/genética , Proteínas Portadoras/genética , Atrofia Muscular Espinal/genética , Artrogriposis/diagnóstico por imagen , Artrogriposis/fisiopatología , Codón sin Sentido/genética , Femenino , Humanos , Recién Nacido , Atrofia Muscular Espinal/diagnóstico por imagen , Atrofia Muscular Espinal/fisiopatología , Secuenciación Completa del GenomaRESUMEN
BACKGROUND: Arthrogryposis multiplex congenita (AMC) is a condition that describes neonates born with ≥2 distinct congenital contractures. Despite spinal deformity in 3% to 69% of patients, inadequate data exist on growth-friendly instrumentation (GFI) in AMC. Our study objectives were to describe current GFI trends in children with AMC and early-onset scoliosis (EOS) and to compare long-term outcomes with a matched idiopathic EOS (IEOS) cohort to determine whether spinal rigidity or extremity contractures influenced outcomes. METHODS: Children with AMC and spinal deformity of ≥30° who were treated with GFI for ≥24 months were identified from a multicenter EOS database (1993 to 2017). Propensity scoring matched 35 patients with AMC to 112 patients with IEOS with regard to age, sex, construct, and curve. Multivariable linear mixed modeling compared changes in spinal deformity and the 24-item Early Onset Scoliosis Questionnaire (EOSQ-24) across cohorts. Cohort complications and reoperations were analyzed using multivariable Poisson regression. RESULTS: Preoperatively, groups did not differ with regard to age (p = 0.87), sex (p = 0.96), construct (p = 0.62), rate of nonoperative treatment (p = 0.54), and major coronal curve magnitude (p = 0.96). After the index GFI, patients with AMC had reduced percentage of coronal correction (35% compared with 44%; p = 0.01), larger residual coronal curves (49° compared with 42°; p = 0.03), and comparable percentage of kyphosis correction (17% compared with 21%; p = 0.52). In GFI graduates (n = 81), final coronal curve magnitude (55° compared with 43°; p = 0.22) and final sagittal curve magnitude (47° compared with 47°; p = 0.45) were not significantly different at the latest follow-up after definitive surgery. The patients with AMC had reduced T1-S1 length (p < 0.001), comparable T1-S1 growth velocity (0.66 compared with 0.85 mm/month; p = 0.05), and poorer EOSQ-24 scores at the time of the latest follow-up (64 compared with 83 points; p < 0.001). After adjusting for ambulatory status and GFI duration, patients with AMC developed 51% more complications (incidence rate ratio, 1.51 [95% confidence interval (CI), 1.11 to 2.04]; p = 0.009) and 0.2 more complications/year (95% CI, 0.02 to 0.33 more; p = 0.03) compared with patients with IEOS. CONCLUSIONS: Patients with AMC and EOS experienced less initial deformity correction after the index surgical procedure, but final GFI curve magnitudes and total T1-S1 growth during active treatment were statistically and clinically comparable with IEOS. Nonambulatory patients with AMC with longer GFI treatment durations developed the most complications. Multidisciplinary perioperative management is necessary to optimize GFI and to improve quality of life in this complex population. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Asunto(s)
Artrogriposis/cirugía , Procedimientos Ortopédicos/métodos , Escoliosis/cirugía , Artrogriposis/complicaciones , Artrogriposis/fisiopatología , Estudios de Casos y Controles , Niño , Preescolar , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Crecimiento , Humanos , Lactante , Modelos Lineales , Modelos Logísticos , Masculino , Procedimientos Ortopédicos/instrumentación , Puntaje de Propensión , Estudios Retrospectivos , Escoliosis/congénito , Escoliosis/etiología , Escoliosis/fisiopatología , Resultado del TratamientoRESUMEN
PURPOSE: Arthrogryposis multiplex congenita (AMC) refers to a large heterogeneous group of conditions involving joint contractures in two or more different areas of the body. Contractures can lead to decreased range of motion and strength, and affect ambulation and autonomy. The aim of this study was to describe the orthopedic interventions and functional outcomes of a large cohort of children with AMC followed in a pediatric orthopedic center. METHODS: A retrospective chart review of all children diagnosed with AMC followed at Shriners Hospital for Children - Canada (SHC) between January 1979 and July 2016 was conducted. One hundred twenty patients were identified, of whom six were excluded due to misdiagnosis or insufficient chart information. One hundred fourteen were retained. Patient demographics, AMC classification, comorbidities, operative and non-operative treatments received as well as community ambulation status, level of autonomy in self-care and transfers at latest follow-up were recorded. RESULTS: There were 54 males and 60 females with a mean age at last clinic visit of 10 years 3 months. Amyoplasia and distal arthrogryposis (DA) were equally represented in our sample, 47 (41.2%) and 49 (43.0%) participants respectively, with the category Other comprising the remaining 18 (15.8%) participants. Children with DA had less involvement of the proximal joints than those in the two other groups. Contractures and deformities of the foot and ankle were the most prevalent, affecting 91.5% with Amyoplasia, 85.7% with DA and 83.3% in the Other category. Contractures of the shoulder and elbow were more common among individuals with Amyoplasia and those categorized Other than those with DA. In terms of walking ability, 98% of participants with DA were independent ambulators. Walking ability varied among the Other participants. Similarly, most children with DA were independent in self-care and transfers at the most recent follow-up. CONCLUSION: The relatively large sample size of this study allowed for a better insight into the challenges associated with AMC management. These findings demonstrated the need for genetic testing to provide accurate diagnosis and classification, along with the use of standardized outcome tools to measure effectiveness of interventions. As AMC is rare, multi-site prospective studies are needed to improve research opportunities, develop functional measures specific to AMC and disseminate findings on a wider scale.
Asunto(s)
Artrogriposis/rehabilitación , Procedimientos Ortopédicos/métodos , Actividades Cotidianas , Adolescente , Artrogriposis/diagnóstico , Artrogriposis/fisiopatología , Niño , Preescolar , Deambulación Dependiente , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Autonomía Personal , Recuperación de la Función , Estudios Retrospectivos , Autocuidado , Resultado del Tratamiento , Adulto JovenRESUMEN
CASE: A 20-year-old man with congenital arthrogryposis presented for evaluation of biceps dysfunction. Although his left elbow was supple with 0° to 110° passive range of motion (ROM), he had no active ROM and was unable to perform basic activities of daily living such as bringing his hand to his mouth to feed himself. A bipolar latissimus transfer was performed to achieve functional active ROM. CONCLUSION: Bipolar latissimus transfer is a challenging, robust flap able to restore active elbow flexion in select groups of patients with biceps dysfunction, supple elbow, and functional latissimus dorsi.
Asunto(s)
Artrogriposis/cirugía , Músculos Superficiales de la Espalda/trasplante , Extremidad Superior/fisiología , Artrogriposis/fisiopatología , Humanos , Masculino , Rango del Movimiento Articular , Adulto JovenRESUMEN
OBJECTIVE: Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) is caused by a heterozygous deletion of peripheral myelin protein-22 (PMP22) gene resulting in focal sensorimotor deficits. Our lab has identified a disruption of myelin junctions in excessively permeable myelin that impairs action potential propagation. This mechanism is expected to cause fatigue in patients with HNPP. Therefore, the objective was to characterize fatigue in patients with HNPP and determine the relationship of fatigue to nerve pathology, disability, and quality of life. METHODS: Nine females with HNPP participated in a single visit that included genotyping, nerve conduction studies, neurological exam, quantitative magnetic resonance imaging, and a physical therapy exam incorporating upper and lower extremity function and survey measures of fatigue. This visit was followed by 2 weeks of ecological momentary assessment (wrist-worn device) that captured fatigue ratings five times per day. RESULTS: Participants demonstrated mild neurological impairment (CMTNS: 5.7 ± 2.8), yet reported high fatigue levels (average fatigue intensity over 2 weeks: 5.9 out of 10). Higher fatigue levels were associated with poorer quality of life and more pain. Higher fatigue was associated with significantly greater distal nerve proton density changes on peripheral nerve MRI, which is in line with hyper-permeable myelin in HNPP. INTERPRETATION: Fatigue is common and severe among patients with HNPP whose disabilities are minimal by conventional outcome measures. Therapeutic interventions targeting fatigue have the potential to improve quality of life and may serve as a robust outcome measure to show longitudinal changes for patients with HNPP.
Asunto(s)
Artrogriposis/complicaciones , Artrogriposis/diagnóstico , Fatiga/diagnóstico , Fatiga/etiología , Neuropatía Hereditaria Motora y Sensorial/complicaciones , Neuropatía Hereditaria Motora y Sensorial/diagnóstico , Adulto , Artrogriposis/fisiopatología , Evaluación Ecológica Momentánea , Fatiga/fisiopatología , Femenino , Genotipo , Neuropatía Hereditaria Motora y Sensorial/fisiopatología , Humanos , Imagen por Resonancia Magnética , Conducción Nerviosa/fisiología , Examen NeurológicoRESUMEN
Arthrogryposis multiplex congenita involves stiff contracture of joints and weak atrophic muscles presenting at birth. The two most common forms are amyoplasia and distal arthrogryposis. Amyoplasia affects all 4 extremities: internally rotated shoulders, extended fixed elbows, flexed fixed wrists, extended fixed knees, clubfeet, and decreased muscle volume. Distal arthrogryposis is a group of syndromes with a genetic basis. The distal joints are contracted. Clubfeet and congenital vertical talus are the most common foot deformities. A 10-year-old boy presented with distal arthrogryposis with bilateral congenital tali. He reported having deformed and painful feet and difficulty wearing shoes. His rocker-bottom foot deformities caused him to walk with a heel to heel gait. He also had stiff extended knees. His previous foot surgeries included failed open reduction and pin fixation of the talonavicular joints with Achilles tendon lengthening and capsulotomies. The boy underwent bilateral talectomies and releases of contracted joint capsules and lengthening of multiple extrinsic tendons through separate incisions. The talectomy of each foot was performed via a novel medial surgical approach. At 2-year follow-up, he had normal-appearing plantar grade feet. He had a painless gait, could ambulate independently, and was considered to have an excellent result. This is the first detailed report of performing a talectomy via a medial approach for bilateral congenital tali in a patient with arthrogryposis multiplex congenita. [Orthopedics. 2020; 43(6):e623-e626.].
Asunto(s)
Artrogriposis/cirugía , Liberación de la Cápsula Articular , Cápsula Articular/cirugía , Procedimientos Ortopédicos/métodos , Astrágalo/cirugía , Caminata/fisiología , Artrogriposis/fisiopatología , Niño , Marcha/fisiología , Humanos , Masculino , Rango del Movimiento Articular/fisiología , Astrágalo/fisiopatología , Resultado del TratamientoRESUMEN
INTRODUCTION: Distal arthrogryposis type 5D (DA5D) is an autosomal recessive disease. The clinical symptoms include contractures of the joints of limbs, especially camptodactyly of the hands and/or feet, unilateral ptosis, a round-shaped face, arched eyebrows, and micrognathia, without ophthalmoplegia. ECEL1 is a DA5D causative gene that encodes a membrane-bound metalloprotease. ECEL1 plays important roles in the final axonal arborization of motor nerves in limb skeletal muscles and neuromuscular junction formation during prenatal development. METHODS: A DA5D family with webbing of the elbows and fingers was recruited. We performed whole-exome sequencing (WES) and filtered mutations by disease-causing genes of arthrogryposis multiplex congenita (AMC). Mutational analysis and cosegregation confirmation were then performed. RESULTS: We identified novel compound heterozygous mutations of ECEL1 (NM_004826: c.69C>A, p.C23∗ and c.1810G>A, p.G604R) in the proband. CONCLUSIONS: We detected causative mutations in a DA5D family, expanding the spectrum of known ECEL1 mutations and contributing to the clinical diagnosis of DA5D.
Asunto(s)
Artrogriposis , Metaloendopeptidasas/genética , Mutación/genética , Oftalmoplejía , Enfermedades de la Retina , Artrogriposis/genética , Artrogriposis/patología , Artrogriposis/fisiopatología , Niño , Análisis Mutacional de ADN , Humanos , Masculino , Oftalmoplejía/genética , Oftalmoplejía/patología , Oftalmoplejía/fisiopatología , Linaje , Polimorfismo de Nucleótido Simple/genética , Enfermedades de la Retina/genética , Enfermedades de la Retina/patología , Enfermedades de la Retina/fisiopatologíaRESUMEN
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited disorder commonly presenting with acute-onset, non-painful focal sensory and motor mono neuropathy. In 80% of cases, the genetic defect is a 1.5âMb deletion on chromosome 17p11.2, including PMP22. Only few cases of partial deletion and point mutations in PMP22 are involved in HNPP. We investigated a 62-years-old man with lower limb plexopathy first considered as Garland's syndrome. A month later, his 29 years old son also consulted for paresthesia on the peroneal nerve.Targeted sequencing of the PMP22 gene identified a c.370delT (p.Trp124Glyfs*31) in both affected patients.We report a new PMP22 point mutation associated with an atypical clinical phenotype of HNPP, a painful plexopathy of the lower limb worsenen by diabetes and a mere paresthesia, but a typical ENMG. This study illustrates the large spectrum of the disease, and emphasizes the importance of a complete ENMG and family history.
Asunto(s)
Artrogriposis/genética , Artrogriposis/fisiopatología , Neuropatía Hereditaria Motora y Sensorial/genética , Neuropatía Hereditaria Motora y Sensorial/fisiopatología , Proteínas de la Mielina/genética , Adulto , Artrogriposis/diagnóstico , Neuropatía Hereditaria Motora y Sensorial/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Mutación PuntualAsunto(s)
Artrogriposis/etiología , Neuropatía Hereditaria Motora y Sensorial/etiología , Poliomielitis/complicaciones , Presión/efectos adversos , Anciano , Artrogriposis/fisiopatología , Mano/irrigación sanguínea , Mano/inervación , Neuropatía Hereditaria Motora y Sensorial/fisiopatología , Humanos , Masculino , Debilidad Muscular/etiología , Debilidad Muscular/fisiopatología , Poliomielitis/fisiopatología , Ultrasonografía/métodosRESUMEN
BACKGROUND: The Ponseti method effectively treats idiopathic clubfoot, but its effectiveness in treating the stiffer clubfoot associated with arthrogryposis is less clear. The purpose of this study was to assess the comparative effectiveness of the Ponseti method in 5-year-old children with either idiopathic clubfoot or clubfoot due to arthrogryposis. METHODS: The outcomes of the Ponseti method were retrospectively evaluated in children with idiopathic clubfoot and clubfoot associated with arthrogryposis. The children with clubfoot were seen at our hospital between 2012 and 2019 and were 4.0 to 6.9 years old at the time of their evaluation. Outcomes of the 2 groups of children with clubfoot were assessed using passive range of motion, foot pressure analysis, the Gross Motor Function Measure Dimension-D, and parent report using the Pediatric Outcomes Data Collection Instrument. These results were also compared with the same measures from a group of typically developing children. Surgical and bracing history was also recorded. RESULTS: A total of 117 children were included (89 idiopathic clubfoot and 28 associated with arthrogryposis) with an average age of 4.8±0.8 years. The historical gait analyses of 72 typically developing children were used as a control, with an average age of 5.2±0.8 years. Significant residual equinovarus was seen in both children with idiopathic clubfoot and associated with arthrogryposis according to passive range of motion and foot pressure analysis when compared with normative data. Children with arthrogryposis demonstrated limited transfer and basic mobility, sports functioning, and global functioning while children with idiopathic clubfoot were significantly different from their typically developing peers in only transfer and basic mobility. CONCLUSIONS: Although children with idiopathic clubfoot continue with some level of residual deformity, the Ponseti method is effective in creating a pain-free, highly functional foot. In children with clubfoot associated with arthrogryposis, the Ponseti method is successful in creating a braceable foot that can delay the need for invasive surgical intervention. LEVEL OF EVIDENCE: Level III, Therapeutic Studies-Investigating the Results of Treatment.
Asunto(s)
Artrogriposis , Moldes Quirúrgicos , Pie Equinovaro , Procedimientos Ortopédicos , Tenotomía , Articulación del Tobillo/fisiopatología , Artrogriposis/complicaciones , Artrogriposis/fisiopatología , Artrogriposis/terapia , Preescolar , Pie Equinovaro/complicaciones , Pie Equinovaro/fisiopatología , Pie Equinovaro/terapia , Pie Equino/diagnóstico , Pie Equino/etiología , Femenino , Análisis de la Marcha , Humanos , Masculino , Procedimientos Ortopédicos/efectos adversos , Procedimientos Ortopédicos/instrumentación , Procedimientos Ortopédicos/métodos , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Rango del Movimiento Articular , Recuperación de la Función , Estudios Retrospectivos , Tenotomía/efectos adversos , Tenotomía/métodosRESUMEN
BACKGROUND: Little is known about patient-reported health status in children and adolescents with arthrogryposis. Utilizing the Patient-Reported Outcome Measurement Information System (PROMIS) and Pediatric Outcomes Data Collection Instrument (PODCI) questionnaires, we investigated functional and psychosocial measures in arthrogryposis. METHODS: A total of 118 patients with arthrogryposis were identified from a prospective longitudinal cohort (the Congenital Upper Limb Difference Registry) from 2014 to 2018. Demographics and patient-reported outcome measures were evaluated, including the PROMIS [upper extremity (UE) function, pain, depression, anxiety, and peer relations] and PODCI questionnaires (UE function, pain, happiness, and global function). RESULTS: A total of 29 arthrogrypotic patients had complete PROMIS and PODCI data. This cohort was divided into distal arthrogryposis and amyoplasia groups, with 15 and 14 patients in each group, respectively. There were 8 males in the distal arthrogryposis group with a median age of 9 years and 7 males in the amyoplasia group with a median age of 8 years. For both cohorts, the median UE function PROMIS scores were significantly below population norms, 31 for distal arthrogryposis and 22 for amyoplasia. PODCI UE function was statistically lower for amyoplasia compared with the distal arthrogryposis cohort. PROMIS pain, depression, anxiety, and peer relations were in the normal range for both amyopasia and distal arthrogryposis. Median PODCI pain and happiness ranged from 85 to 88 for all patients with no statistical difference between groups. CONCLUSIONS: Arthrogryposis patients have lower UE function scores compared with population normals, but they have emotional states that are consistent with populations norms. Amyoplasia patients were functionally worse than distal arthrogryposis patients. LEVELS OF EVIDENCE: Level II.
Asunto(s)
Artrogriposis , Rendimiento Físico Funcional , Funcionamiento Psicosocial , Artrogriposis/epidemiología , Artrogriposis/fisiopatología , Artrogriposis/psicología , Niño , Femenino , Humanos , Estudios Longitudinales , Masculino , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , Sistema de Registros/estadística & datos numéricos , Encuestas y Cuestionarios , Estados Unidos/epidemiología , Extremidad Superior/fisiopatologíaRESUMEN
BACKGROUND: Congenital arthrogryposis (CA) consists of congenital joint contractures that affect at least two joints in different parts of the body. Approximately, 80% of CA cases are neurogenic, with changes to the formation, structure or functioning of the central and/or peripheral nervous systems. Most abnormalities are triggered either by motoneurons decreased activation in the corticospinal tract or by direct motoneurons injury. There had been few reports in the literature correlating congenital infection in humans with arthrogryposis until 2015. CA has recently been described associated with congenital Zika syndrome (CZS). METHODS: The objective of this study was to investigate and describe accurately the arthrogrypotic alterations in infants diagnosed with CZS and thus, suggest a possible pattern of orthopedic impairment. A total of 198 medical records of infants with CZS were evaluated. According to inclusion and exclusion criteria, 17 infants were included in the present study. Arthrogrypotic joints were orthopedically evaluated in four segments: right, left, upper, and lower limbs. All the four segments were assessed independently. RESULTS: Flexed wrists were the most frequently observed manifestation, associated with ulnar deviation (35.29%). Deformities were also commonly found in the third and fourth fingers (64.70%). Hip dislocation was found in 58.82% of the patients and talipes equinovarus and equinovalgus ankles were found in 29.41 and 23.52%. CONCLUSION: There was a particular pattern of joint impairment related to CZS and arthogrypotic alterations of infants evaluated in this study.
Asunto(s)
Artrogriposis/complicaciones , Artrogriposis/fisiopatología , Infección por el Virus Zika/complicaciones , Artrogriposis/virología , Brasil/epidemiología , Femenino , Enfermedades Fetales , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo , Virus Zika/patogenicidad , Infección por el Virus Zika/fisiopatología , Infección por el Virus Zika/virologíaRESUMEN
X-linked infantile spinal muscular atrophy (SMAX2), OMIM 301830, is a rare, severe form of spinal muscular atrophy, caused by variants in the Ubiquitin like modifier-activating enzyme 1 (UBA1) gene. Clinical features reported to date include marked hypotonia, areflexia, arthrogryposis, contractures, myopathic facies and tongue fibrillations. Previous reports have included a history of contractures. We report a male patient presenting following a normal pregnancy with typical symptoms of X-linked infantile spinal muscular atrophy including hypotonia, weakness, areflexia and respiratory insufficiency, however contractures were absent. There was a significant family history of neuromuscular disease on the maternal side, with several male relatives all dying before the age of six months. Creatine Kinase was mildly elevated, MRI Brain was normal and neurophysiological testing revealed a diffuse motor neuronopathy. Genetic testing for SMN1 gene was normal. UBA1 sequencing revealed a maternally inherited hemizygous familial variant [c.1681G>A p. (Asp561Asn)], which has not been previously reported.
Asunto(s)
Artrogriposis/genética , Artrogriposis/fisiopatología , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/fisiopatología , Enzimas Activadoras de Ubiquitina/genética , Artrogriposis/complicaciones , Artrogriposis/etiología , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Humanos , Lactante , Masculino , Mutación , FenotipoRESUMEN
Arthrogryposis multiplex congenita (AMC) is defined as congenital, non-progressive contractures in more than two joints and in multiple body areas, resulting from reduced fetal mobility. So far, more than 400 causative genes for AMC have been identified. Some isolated AMC phenotypes arise as a result of mutations in genes encoding components required for motor neuron structure, function, and myelination, as in the case of ADCY6 encoding the enzyme adenylyl cyclase type 6. ADCY6 inactivation, due to biallelic variants, have been previously associated with the lethal congenital contracture syndrome 8 (LCCS8). So far, only four LCCS8 patients, from two families, have been reported. Here, we describe a new patient affected by a severe form of AMC, harboring two novel compound heterozygous variants in ADCY6. Our findings expand the clinical and mutational spectrum of LCCS8, showing a possible correlation between the impact of the ADCY6 missense variants reported to date, predicted by molecular modeling, and the severity of the phenotype.
Asunto(s)
Adenilil Ciclasas/genética , Artrogriposis/genética , Predisposición Genética a la Enfermedad , Artrogriposis/fisiopatología , Preescolar , Femenino , Estudios de Asociación Genética , Humanos , Lactante , Masculino , Mutación Missense/genética , Linaje , Fenotipo , Secuenciación del ExomaRESUMEN
BACKGROUND: Hereditary neuropathy with liability to pressure palsies (HNPP) is a rare neuropathy with a heterogeneous clinical profile. Painless recurrent palsies are the usual presentation, but neuropathic pain could be predominant or inaugural. Browsing the medical literature, we only found two articles reffering to this important clinical feature. Whether there are differences between patients with or without pain is unclear. The main objective of this study was to compare the clinical and electrophysiological features of these patients and to evaluate the impact on their disability. METHODS: All patients diagnosed with HNPP at the Limoges University Hospital Centre were included and separated into two groups according to the presence or absence of neuropathic pain. In each case, the clinical, genetic, electrodiagnostic, therapeutic features and the modified Rankin Scale (mRS) were evaluated. RESULTS: Out of 23 patients, 52% presented with neuropathic pain. There was no difference between groups regarding to clinical and electrophysiological features, except for the amplitude of the ulnar sensory nerve (p < 0,003). The amplitudes of sensory nerve action potentials (SNAPs) seemed to be higher in patients with pain, but were below the lower limit of normal. Patients with pain had a higher mRS than patients without pain (p < 0,007). CONCLUSION: This study supports previous published results and highlights a trend for higher sensory amplitudes in HNPP patients with pain. We found a prevalence of neuropathic pain of 52% in patients with HNPP, underlining the need to systematically assess pain in such patients in order to improve their management.
Asunto(s)
Artrogriposis/diagnóstico , Artrogriposis/fisiopatología , Fenómenos Electrofisiológicos/fisiología , Neuropatía Hereditaria Motora y Sensorial/diagnóstico , Neuropatía Hereditaria Motora y Sensorial/fisiopatología , Dolor/diagnóstico , Dolor/fisiopatología , Adolescente , Adulto , Anciano , Artrogriposis/epidemiología , Niño , Preescolar , Estudios de Cohortes , Femenino , Neuropatía Hereditaria Motora y Sensorial/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Dolor/epidemiología , Estudios Retrospectivos , Adulto JovenRESUMEN
Knee-flexion deformity in arthrogryposis multiplex congenita is treated by serial casting into extension, distal femoral osteotomies, distal femoral-guided growth, hemiepiphysiodesis, external fixation, capsulotomy, and soft-tissue releases. We are aware of four cases treated by distal anterior femoral-guided growth with tension band plates in which an unreported complication occurred: the screws of the tension band plates penetrated the posterior cortex of the femur during remodeling with metaphyseal funnelization risking the neurovascular bundle. Inclusion criteria were cases with arthrogryposis multiplex congenita and knee-flexion deformity, treatment at our institution by distal anterior femoral-guided growth with tension band plates, and radiographic evidence of posterior cortex screw penetration during remodeling from growth. Six knees (four cases) met the inclusion criteria. The average age at the distal anterior femoral-guided growth with tension band plate operation was 5.8 years. Radiographs after 6.6 years of follow-up showed that the screws of the tension band plates, which at surgery were intrametaphyseal, had penetrated the posterior cortex of the femur. Four knees (two cases) had diffuse pain around the knee to lower leg area, and instrumentation removal alleviated the symptoms. During distal anterior femoral-guided growth with tension band plate operation for knee-flexion deformity in arthrogryposis multiplex congenita, we found that the screws of the tension band plates, which were initially located inside the metaphysis, may protrude through the posterior bone cortex during metaphyseal funnelization with growth, and may encroach upon the neurovascular tissues. Level of evidence: Level IV - case series.
Asunto(s)
Artrogriposis/rehabilitación , Placas Óseas , Tornillos Óseos , Regeneración Tisular Dirigida/métodos , Articulación de la Rodilla/cirugía , Osteotomía/métodos , Rango del Movimiento Articular/fisiología , Artrogriposis/diagnóstico , Artrogriposis/fisiopatología , Artrogriposis/cirugía , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiopatología , Masculino , Radiografía , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
The aim of this study was to examine the effectiveness of Ilizarov method in severe congenital flexion deformity of the knee. This was a retrospective study of eight consecutive bilateral cases (five girls and three boys, with mean age of 4 years, involving 16 knees) with minimum 2-year follow-up. Four patients had multiple congenital contractures and two patients each had popliteal pterygium syndrome and complete tibial hemimelia. All patients were treated with Ilizarov fixator and gradual correction (additional soft tissue releases in three knees). Six patients had bilateral foot and ankle deformity treated with the same fixator, and cases with tibial hemimelia had centralization of fibula and quadriceps reconstruction. Flexion deformity could be corrected in all cases. Mean duration of dynamic phase was 78.5 (55-108) days, that of static phase was 42.4 (7-100) days, and total duration of external fixation was 120.9 (87-186) days. At mean follow-up of 34.5 (23-60) months, flexion deformity improved from the preoperative value of 74.9° (50°-130°) to 13.7° (10°-16°), and passive arc of motion of knee improved from the preoperative value of 38.8° (20°-55°) to 83.6° (55°-110°). Both were statistically significant (P < 0.0001). All patients (previously nonambulatory) were ambulatory with brace and support. All patients faced pin-tract and skin complications that were successfully managed. Ilizarov method is effective in severe congenital flexion deformity of the knee in improving ambulatory status. Realignment of quadriceps mechanism and limb mechanical axis (including ankle and foot deformities) must be given due importance. Minor recurrences of deformity must be expected in all cases.