RESUMO
A 15-year-old boy with a terminal deletion of the short arm of chromosome 4 is described. The patient has a mild clinical phenotype that is incompatible with Wolf-Hirschhorn syndrome. Careful neurological examination including CT scan did not show any signs of Huntington disease. The chromosomal breakpoint was analyzed by means of polymorphic DNA probes localized close to the tentative Huntington (HD) locus. The breakage has occurred between D4S43 and D4S90 loci and thus deletes part of the chromosomal candidate regions for the HD locus.
Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Cromossomos Humanos Par 4 , Doença de Huntington/genética , Convulsões/genética , Adolescente , Bandeamento Cromossômico , Sondas de DNA , Ligação Genética , Humanos , Cariotipagem , Masculino , Fenótipo , Convulsões/tratamento farmacológico , Síndrome , Translocação Genética , Ácido Valproico/uso terapêuticoRESUMO
BACKGROUND: Extensive cerebral calcifications and leukoencephalopathy have been reported in two rare disorders Coats plus and leukoencephalopathy with calcifications and cysts. In the latter, a progressive formation of parenchymal brain cysts is a special feature, whereas Coats plus is characterized by intrauterine growth retardation, bilateral retinal telangiectasias and exudations (Coats disease), sparse hair, and dysplastic nails without cyst formation. METHODS: We identified 13 patients, including two pairs of siblings, with extensive cerebral calcifications and leukoencephalopathy. We reviewed clinical, ophthalmologic, radiologic and neuropathologic data of seven deceased patients and studied five patients prospectively. RESULTS: Eleven patients were small for gestational age; the other symptoms emerged from infancy to adolescence. All patients had neurologic symptoms including seizures, spasticity, dystonia, ataxia, and cognitive decline. Progressive intracerebral calcifications involved deep gray nuclei, brainstem, cerebral and cerebellar white matter, and dentate nuclei and were accompanied by diffuse white matter signal changes and, in five patients, cerebral cysts. Eleven patients had retinal telangiectasias or angiomas. Additional features were skeletal and hematologic abnormalities, intestinal bleeding, and poor growth. Neuropathologic examination showed extensive calcinosis and abnormal small vessels with thickened, hyalinized wall and reduced lumen. CONCLUSIONS: Our data suggest that Coats plus syndrome and leukoencephalopathy with calcifications and cysts belong to the same spectrum. The primary abnormality seems to be an obliterative cerebral angiopathy involving small vessels, leading to dystrophic calcifications via slow necrosis and finally to formation of cysts and secondary white matter abnormalities.
Assuntos
Encefalopatias/etiologia , Calcinose/etiologia , Transtornos Cerebrovasculares/complicações , Cistos/etiologia , Doenças Retinianas/complicações , Vasos Retinianos , Adolescente , Doenças Ósseas/diagnóstico por imagem , Doenças Ósseas/etiologia , Encefalopatias/diagnóstico , Calcinose/diagnóstico , Calcinose/patologia , Transtornos Cerebrovasculares/patologia , Pré-Escolar , Feminino , Hemangioma/complicações , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/etiologia , Imageamento por Ressonância Magnética , Masculino , Microcirculação , Doenças Retinianas/diagnóstico , Neoplasias da Retina/complicações , Síndrome , Telangiectasia/complicações , Tomografia Computadorizada por Raios XRESUMO
A case of early-onset, severe spinal muscular atrophy is reported. Normal fetal breathing movement patterns and heart rate accelerations were observed in spite of the severe hypotonia evident at birth.
Assuntos
Doenças Fetais/fisiopatologia , Atrofias Musculares Espinais da Infância/fisiopatologia , Adulto , Evolução Fatal , Feminino , Movimento Fetal/fisiologia , Frequência Cardíaca Fetal/fisiologia , Humanos , Recém-Nascido , Masculino , Gravidez , Respiração/fisiologiaRESUMO
We investigated the integrity of striatal dopaminergic system in seven patients with dopa-responsive dystonia (DRD). Dopamine transporter function ([(11)C]CFT) and D1 ([(11)C]NNC 756) and D2 receptors ([(11)C]raclopride) were studied in same patients using positron emission tomography. Compared to age-adjusted control values the dopamine D2 receptor availability was increased in DRD. The mean age-adjusted [(11)C]raclopride uptake was 116% of the control mean in the putamen (p = 0.004) and 114% in the caudate nucleus (p = 0.007). The mean [(11)C]NNC 756 uptake was not different between DRD patients and controls, the age-adjusted uptake in DRD being 93% of mean control value in the putamen (p = 0.20) and 95% in the caudate nucleus (p = 0.40). The dopamine transporter binding was not altered. The [(11)C]CFT uptake in DRD was 96% of the control value in the putamen (p = 0.64), and 95% in the caudate nucleus (p = 0.44). In conclusion, striatal dopamine D2 receptors availability is increased in DRD whereas dopamine D1 receptors and dopamine transporter ligand binding is unchanged. The pattern of changes in striatal dopaminergic system in DRD is different from that reported in juvenile Parkinson's disease. The increased D2 receptor availability may be due to reduced competition by endogenous dopamine or a compensatory response to dopamine deficiency, or both.