RESUMEN
Although whole-exome sequencing (WES) is the gold standard for the diagnosis of neurodevelopmental disorders (NDDs), it remains expensive for some genetic centers. Commercialized panels comprising all OMIM-referenced genes called "medical exome" (ME) constitute an alternative strategy to WES, but its efficiency is poorly known. In this study, we report the experience of 2 clinical genetic centers using ME for diagnosis of NDDs. We recruited 216 consecutive index patients with NDDs in 2 French genetic centers, corresponded to the daily practice of the units and included non-syndromic intellectual disability (NSID, n = 33), syndromic ID (NSID = 122), pediatric neurodegenerative disorders (n = 7) and autism spectrum disorder (ASD, n = 54). We sequenced samples from probands and their parents (when available) with the Illumina TruSight One sequencing kit. We found pathogenic or likely pathogenic variants in 56 index patients, for a global diagnostic yield of 25.9%. The diagnosis yield was higher in patients with ID as the main diagnosis (32%) than in patients with ASD (3.7%). Our results suggest that the use of ME is a valuable strategy for patients with ID when WES cannot be used as a routine diagnosis tool.
Asunto(s)
Secuenciación del Exoma , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Trastornos del Neurodesarrollo/genética , Adolescente , Adulto , Alelos , Niño , Preescolar , Biología Computacional/métodos , Femenino , Estudios de Asociación Genética/métodos , Humanos , Lactante , Patrón de Herencia , Masculino , Persona de Mediana Edad , Trastornos del Neurodesarrollo/diagnóstico , Fenotipo , Análisis de Secuencia de ADN/métodos , Adulto JovenAsunto(s)
Hipertonía Muscular/genética , Proteínas Musculares/genética , Mutación Missense , Canales de Sodio/genética , Análisis Mutacional de ADN , Femenino , Humanos , Recién Nacido , Isoleucina/genética , Masculino , Hipertonía Muscular/patología , Hipertonía Muscular/fisiopatología , Canal de Sodio Activado por Voltaje NAV1.4 , Fenotipo , Treonina/genéticaRESUMEN
Epilepsy is a repetition of seizures. It is frequent child pathology: 40% of all epileptic people have less than 15 years of age. Seizures appear on a developing brain. Treatment must avoid frequent and long lasting seizures but at the same time must spare cognitive development. New antiepileptic drugs seem to have more specialized indications, less side effects and thus represent a very interesting tool for neuropediatrician. Monotherapy has to be preferred as often as possible to assure good cognitive function.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Anticonvulsivantes/farmacología , Humanos , LactanteRESUMEN
Primary infection with human herpesvirus-6 (HHV-6) causes the classical roseola infantum. Otherwise the infection is clinically silent but it may sometimes be responsible for central nervous system involvement. In order to illustrate such a type of lesions, we report on a 16-month-old girl with acute leucoencephalitis. The disease started with pyrexia 40 degrees C, followed by an episode of seizure, erythematous rash on the trunk and then coma. Brain MRI showed wide lesions on white matter. HHV-6 DNA was detected by PCR in the CSF and serum at the acute stage, and tests for HHV-6 antibody showed a significant increase of IgG antibody titre between acute and convalescent sera. One month later complete clinical recovery was observed while the MRI showed a partial disappearance of the lesions. The sero-conversion associated with the detection of the viral DNA in the serum identified a primary HHV-6 infection and the detection of viral nucleic acid in CSF gives arguments for the responsibility of the virus in the pathogenesis. When facing an acute leuco-encephalitis in infants, it is important to perform exhaustive virology investigations to rule out the implication of HHV-6 as well as other commonly incriminated pathogens (EBV, CMV, mycoplasma, enterovirus) to avoid accusing wrongly the vaccines.
Asunto(s)
Encefalitis Viral/diagnóstico , Herpesvirus Humano 6/aislamiento & purificación , Infecciones por Roseolovirus/diagnóstico , Encéfalo/patología , Encéfalo/virología , Coma/virología , ADN Viral/sangre , ADN Viral/líquido cefalorraquídeo , Encefalitis Viral/terapia , Femenino , Fiebre/virología , Humanos , Lactante , Imagen por Resonancia Magnética , Infecciones por Roseolovirus/terapia , Convulsiones/virologíaRESUMEN
UNLABELLED: Spinal epidural hematoma is an uncommon complication in hemophilia. CASE REPORTS: The cases of an extensive epidural hematoma in two boys with severe hemophilia are reported. CONCLUSION: Acute onset of severe neck pain or backache leads to the diagnosis of epidural hematoma in children with hemophilia, even in the absence of neurologic symptoms. Early diagnosis is important and relies on magnetic resonance imaging. Replacement therapy is mandatory and must be prescribed before neuroradiologic imaging. Generally, children have a good neurologic outcome.