RESUMO
The objective of this work was to study the natural history of dystrophinopathies and the genotype-phenotype correlations made possible by the development of the clinical part of the French DMD database. The collection of 70,000 clinical data for 600 patients with an average longitudinal follow-up of 12years enabled clarification of the natural history of Duchenne and Becker muscular dystrophies and clinical presentations in symptomatic females. We were able to specify the phenotypic heterogeneity of motor, orthopedic and respiratory involvements (severe, standard and intermediary form), of the cardiac disorder (severe, standard or absent cardiomyopathy, absence of correlation between motor and cardiac involvements), and of brain function (mental deficiency in the patients with Becker muscular dystrophy, psychopathological disorders in dystrophinopathies). Phenotypic variability did not correlate with a specific mutational spectrum. We propose a model of phenotypic analysis based on the presence or not of muscular and cardiac involvements (described by age at onset and rate of progression) and brain involvement (described by the type and the severity of the cognitive impairment and of the psychological disorders). The methodology developed for the DMD gene can be generalized and used for other databases dedicated to genetic diseases. Application of this model of phenotypic analysis for each patient and further development of the database should contribute substantially to clinical research providing useful tools for future clinical trials.
Assuntos
Distrofina/genética , Estudos de Associação Genética , Heterogeneidade Genética , Distrofia Muscular de Duchenne/genética , Adolescente , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Feminino , França/epidemiologia , Técnicas Genéticas , Humanos , Masculino , Atividade Motora , Distrofia Muscular de Duchenne/epidemiologia , FenótipoRESUMO
We reviewed 11 pediatric cases of diaphragmatic paralysis related to nonspinal-cord injury which were managed in our Intensive Care Unit over the past 10 years. Three cases were secondary to birth trauma, 7 followed surgical procedures for congenital heart disease, and 1 occurred in association with injuries sustained in a motor vehicle accident. The paralysis was bilateral in 8 children. The diagnosis was initially suspected on clinical grounds because of respiratory distress, impossibility of weaning from the ventilator, and paradoxical abdominal respiratory movements. Confirmatory investigations included chest radiography, which revealed elevation of the affected hemidiaphragm, fluoroscopy and ultrasound, both of which demonstrated diminished diaphragmatic movement. Electromyography exhibited a failure of diaphragmatic response to phrenic nerve stimulation in 8 patients. All patients were mechanically ventilated; tracheostomy was required in 5 patients. Physiotherapy was considered a beneficial adjuvant measure. Diaphragmatic plication was attempted without success in 3 children. Seven children recovered without sequelae: Partial respiratory autonomy was achieved after an average of 2.6 months, complete autonomy after an average of 5.4 months. Two patients developed chronic lung disease; one of them remains unresponsive, and one child died following accidental extubation. We conclude that the diagnosis of diaphragmatic paralysis is predominantly clinical, and that the outcome of patients treated by adequate endotracheal mechanical ventilation is usually favorable.
Assuntos
Paralisia Respiratória/diagnóstico , Pré-Escolar , Diafragma/lesões , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Complicações do Trabalho de Parto/diagnóstico , Complicações do Trabalho de Parto/terapia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/terapia , Gravidez , Respiração Artificial , Paralisia Respiratória/etiologia , Paralisia Respiratória/terapiaRESUMO
Distal spinal-muscular atrophy 1 (DSMA1) or spinal-muscular atrophy with respiratory distress type 1 (SMARD1) is a rare neuromuscular disorder resulting from IGHMBP2 mutations. It is an autosomal recessive disease. We present the case of a 1-year-old girl admitted for respiratory failure associated with pneumonia. Right hemidiaphragmic elevation on the chest radiograph and distal retractions suggested the diagnosis of DSMA1. It was confirmed by muscle biopsy and molecular analysis. This unrecognized diagnosis should be considered when respiratory failure develops in the first year of life and is associated with diaphragmatic paralysis and distal muscle atrophy. Electromyography with measurement of nerve conduction velocity and muscle biopsy suggest the diagnosis, which must be confirmed by genetic analysis. After identifying the mutations, it is possible to perform prenatal diagnosis.
Assuntos
Insuficiência Respiratória/etiologia , Atrofias Musculares Espinais da Infância/complicações , Biópsia , Proteínas de Ligação a DNA/genética , Eletromiografia , Feminino , Humanos , Lactente , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Mutação , Pneumonia/complicações , Paralisia Respiratória/complicações , Paralisia Respiratória/genética , Atrofias Musculares Espinais da Infância/diagnóstico , Atrofias Musculares Espinais da Infância/genética , Fatores de Transcrição/genéticaAssuntos
Bartonella henselae/isolamento & purificação , Doença da Arranhadura de Gato/microbiologia , Anticorpos Antibacterianos/isolamento & purificação , Doença da Arranhadura de Gato/diagnóstico , Doença da Arranhadura de Gato/tratamento farmacológico , Criança , Febre/complicações , Humanos , Masculino , Reação em Cadeia da Polimerase , RNA Bacteriano/análise , RNA Ribossômico 16S/análise , Rifampina/uso terapêuticoRESUMO
Five cases of central congenital hypoventilation, Ondine's curse, were studied. The diagnostic criteria were: lack of respiratory autonomy during sleep, abnormal CO2 test results and abnormal respiratory monitoring results during sleep. This hypoventilation induced chronic complications, such as a pulmonary arterial hypertension and psychomotor and/or growth retardation. The other conditions frequently associated with Ondine's curse were: brainstem disturbances, Hirschsprung disease and neuroblastoma. Since other brainstem dysfunctions are sometimes associated with hypoventilation and because complications can arise, these children routinely underwent complementary investigations. Treatment was symptomatic. Assisted mechanical ventilation was initiated as soon as possible and carefully monitored. The prognosis for these children has greatly improved and some of them lead a normal life with nightly assisted ventilation at home.
Assuntos
Síndromes da Apneia do Sono/diagnóstico , Idade de Início , Catecolaminas/urina , Pré-Escolar , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Humanos , Lactente , Recém-Nascido , Polissonografia , Prognóstico , Transtornos Psicomotores/etiologia , Respiração Artificial/efeitos adversos , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/cirurgia , Sono REM , Traqueostomia , Resultado do TratamentoRESUMO
We report a case of necrotizing glomerulonephritis with linear fixation along the glomerular basement membrane (GBM) atypical by: 1) the absence of significant renal failure or evidence of pulmonary involvement; 2) no detectable circulating anti GBM antibody by indirect immunofluorescence or radioimmunoassay.
Assuntos
Anticorpos/análise , Glomerulonefrite/imunologia , Glomérulos Renais/imunologia , Adulto , Membrana Basal/imunologia , Humanos , MasculinoRESUMO
In some patients with stable or very gradually worsening neuromuscular disorders, walking performance nevertheless decreases with increasing hip flexion and spinal deformity as the patient grows. The relations between muscular deficiency, pelvic and spinal deformity, head stability, gravity parameters and walking performance were studied in 43 patients aged 18 months to 38 years with a view to finding out how these parameters are related, whether progressive spinal deformity and loss of walking can be avoided or delayed, and whether specific therapy for each of these parameters can help. Early combating of hip flexion deformity by physiotherapy, accompanied by limbering-up exercises of the spine to counteract lumbar and thoracic lordosis are useful, as are orthoses to correct pelvic tilt anteversion, spinal lordosis and head instability. If physiotherapy is ineffectual or too late, tenoctomy of the rectus femoris may help.