RESUMEN
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disease characterized by early infantile macrocephaly and delayed motor and cognitive deterioration. Magnetic resonance imaging (MRI) shows diffusely abnormal and swollen cerebral white matter and subcortical cysts. On follow-up, atrophy ensues. Approximately 80% of MLC patients have mutations in MLC1. We report 16 MLC patients without MLC1 mutations. Eight retained the classical clinical and MRI phenotype. The other 8 showed major MRI improvement. They lacked motor decline. Five had normal intelligence; 3 displayed cognitive deficiency. In conclusion, 2 phenotypes can be distinguished among the non-MLC1 mutated MLC patients: a classical and a benign phenotype.
Asunto(s)
Quistes/genética , Leucoencefalopatías/genética , Leucoencefalopatías/patología , Proteínas de la Membrana/genética , Mutación/genética , Adolescente , Adulto , Encefalopatías/complicaciones , Encefalopatías/patología , Niño , Quistes/complicaciones , Análisis Mutacional de ADN , Femenino , Estudios de Seguimiento , Humanos , Leucoencefalopatías/complicaciones , Imagen por Resonancia Magnética/métodos , Masculino , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To assess health and neurodevelopmental outcome at 3 years of age in neonatal intensive care unit (NICU)-surviving children who were born at 26 or fewer weeks of gestation in a geographically defined region of Belgium from 1999 through 2000. METHODS: The study included a clinical examination and a standardized neurologic and developmental assessment. Disabilities were defined by international criteria. In 97% (92 of 95) of the children, accurate information on the presence of overall disability could be collected. RESULTS: Thirty-six percent (95% confidence interval [CI] 25-47%) of the formally assessed children (28 of 77) had deficient neuromotor development, with 5% of them showing severe sensory-communicative impairment. Mean (+/-standard deviation) scores on the Mental Developmental Index and Psychomotor Developmental Index were 81.2 (18.8) and 73.2 (17.8), respectively. Seventy percent (95% CI 60-80%) had a mental (Mental Developmental Index) or psychomotor (Psychomotor Developmental Index) impairment or both, assessed to be more than 1 standard deviation below the population mean. Mental and psychomotor outcome did not differ significantly when compared according to either gestational age, gender, or multiple birth (all P>.05). When either minor central dysfunction or cerebral palsy was not taken into account, normal mental development was recorded in 62% of the subjects. The cumulative of poor outcome (ie, disability- or prematurity-related death) among the 95 infants discharged alive was estimated to be 58% (95% CI 48-68%), representing 25 (26%) mildly-to-moderately disabled and 28 (29%) severely disabled toddlers, including two infants whose postdischarge deaths were directly related to prematurity. CONCLUSION: The average developmental outcome is poor in children born as extremely preterm infants. Finding early predictors of adverse outcome is a major challenge.
Asunto(s)
Desarrollo Infantil/fisiología , Recien Nacido Prematuro/crecimiento & desarrollo , Enfermedades del Sistema Nervioso/epidemiología , Sistema Nervioso/crecimiento & desarrollo , Bélgica/epidemiología , Preescolar , Femenino , Humanos , Recién Nacido , Embarazo , Segundo Trimestre del Embarazo , PronósticoRESUMEN
Severe myoclonic epilepsy in infancy, or Dravet syndrome, is one of the catastrophic epilepsy syndromes. In the past, treatment was mainly based on valproate and phenobarbital. Recently, some of the new antiepilepsy drugs, such as topiramate and stiripentol, have been shown to be promising in the treatment of this epilepsy syndrome. The treatment regimen of 12 children with Dravet syndrome and proven mutations in the alpha subunit of the sodium channel SCN1A is reported here. Five patients on the "traditional" treatment regimen are compared with seven children on an "optimal" treatment regimen based on a combination of valproate and topiramate. With respect to the literature and our own experience, we propose guidelines for "optimal" treatment of children with severe myoclonic epilepsy in infancy. This includes prevention of hyperthermia, rigorous treatment of fever, avoiding stressful situations, maintenance treatment based on a combination of only two antiepilepsy drugs (ie, valproate and topiramate), and a strict acute seizure treatment based on benzodiazepines. To prevent long-lasting periods of status epilepticus, this acute seizure treatment must be taught to parents and caregivers.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Benzodiazepinas/uso terapéutico , Epilepsia Mioclónica Juvenil/tratamiento farmacológico , Epilepsia Mioclónica Juvenil/patología , Adolescente , Niño , Preescolar , Análisis Mutacional de ADN , Quimioterapia Combinada , Femenino , Fiebre/complicaciones , Fiebre/terapia , Humanos , Masculino , Epilepsia Mioclónica Juvenil/prevención & control , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Canales de Sodio/genética , Estrés Psicológico , Resultado del Tratamiento , Subunidad beta-1 de Canal de Sodio Activado por VoltajeRESUMEN
In a developmentally delayed girl with an autism spectrum disorder, Single nucleotide polymorphism (SNP) array analysis showed a de novo 280 kb deletion on chromosome 16q23.2 involving two genes, GAN and CMIP. Inactivating mutations in GAN cause the autosomal recessive disorder giant axonal neuropathy, not present in our patient. CMIP was recently implicated in the etiology of specific language impairment by genome-wide association analysis. It modulates phonological short-term memory and hence plays an important role in language acquisition. Overlaps of specific language impairment and autism have been debated in the literature regarding the phenotypical language profile as well as etiology. Our patient illustrates that haploinsufficiency of CMIP may contribute to autism spectrum disorders. Our finding further supports the existence of a genetic overlap in the etiology of specific language impairment and autism.