RESUMO
INTRODUCTION/AIMS: We studied a patient with a congenital myasthenic syndrome (CMS) caused by a dominant mutation in the synaptotagmin 2 gene (SYT2) and compared the clinical features of this patient with those of a previously described patient with a recessive mutation in the same gene. METHODS: We performed electrodiagnostic (EDX) studies, genetic studies, muscle biopsy, microelectrode recordings and electron microscopy (EM). RESULTS: Both patients presented with muscle weakness and bulbar deficits, which were worse in the recessive form. EDX studies showed presynaptic failure, which was more prominent in the recessive form. Microelectrode studies in the dominant form showed a marked reduction of the quantal content, which increased linearly with higher frequencies of nerve stimulation. The MEPP frequencies were normal at rest but increased markedly with higher frequencies of nerve stimulation. The EM demonstrated overdeveloped postsynaptic folding, and abundant endosomes, multivesicular bodies and degenerative lamellar bodies inside small nerve terminals. DISCUSSION: The recessive form of CMS caused by a SYT2 mutation showed far more severe clinical manifestations than the dominant form. The pathogenesis of the dominant form likely involves a dominant-negative effect due to disruption of the dual function of synaptotagmin as a Ca2+ -sensor and modulator of synaptic vesicle exocytosis.
Assuntos
Mutação/genética , Síndromes Miastênicas Congênitas/genética , Junção Neuromuscular/genética , Sinaptotagmina II/genética , Adulto , Pré-Escolar , Feminino , Humanos , Síndrome Miastênica de Lambert-Eaton/genética , Síndrome Miastênica de Lambert-Eaton/fisiopatologia , Masculino , Debilidade Muscular/genética , Debilidade Muscular/fisiopatologia , Síndromes Miastênicas Congênitas/diagnóstico , Junção Neuromuscular/fisiopatologiaRESUMO
Von Hippel-Lindau disease is a genetic condition due to mutation of the Von Hippel-Lindau gene, which leads to an increased risk in the development of hemangioblastomas of the brain and spinal cord. The pathophysiology of disease and its clinical manifestations, as they pertain to the general neurologist, are discussed. Therapeutic management of central nervous system hemangioblastomas ranging from neurosurgical resection, radiation therapy, and systemic therapies is reviewed.