RESUMO
Missense mutations in kinesin family member 5A (KIF5A) cause spastic paraplegia 10. We report on 2 patients with de novo stop-loss frameshift variants in KIF5A resulting in a novel phenotype that includes severe infantile onset myoclonus, hypotonia, optic nerve abnormalities, dysphagia, apnea, and early developmental arrest. We propose that alteration and elongation of the carboxy-terminus of the protein has a dominant-negative effect, causing mitochondrial dysfunction in the setting of an abnormal kinesin "motor." These results highlight the role of expanded testing and whole-exome sequencing in critically ill infants and emphasize the importance of accurate test interpretation. Ann Neurol 2016;80:633-637.
Assuntos
Cinesinas/genética , Doenças Mitocondriais/genética , Mioclonia/genética , Apneia/genética , Pré-Escolar , Transtornos de Deglutição/genética , Deficiências do Desenvolvimento/genética , Evolução Fatal , Feminino , Mutação da Fase de Leitura , Humanos , Lactente , Masculino , Doenças Mitocondriais/complicações , Hipotonia Muscular/genética , Mutação , Nervo Óptico/anormalidadesAssuntos
Olho/patologia , Mucormicose/diagnóstico , Doenças Orbitárias/microbiologia , Criança , Dacriocistite/diagnóstico , Dacriocistite/tratamento farmacológico , Drenagem , Olho/microbiologia , Feminino , Humanos , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Hifas/isolamento & purificação , Mucorales/efeitos dos fármacos , Mucorales/crescimento & desenvolvimento , Mucorales/isolamento & purificação , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Doenças Orbitárias/diagnóstico , Doenças Orbitárias/diagnóstico por imagem , Doenças Orbitárias/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Primary brain sarcomas are rarely curable with surgery and standard radiation therapy. They typically recur locally within 6 months of treatment. This case report describes a novel treatment approach for primary or recurrent brain sarcomas with intracavitary brachytherapy. CASE DESCRIPTION: This 34-year-old female presented with a large and rapidly recurrent primary fibrosarcoma in the right fronto-parietal brain only 1 month postinitial total resection. She was reoperated, again with an MRI-documented gross total resection, but at this second surgery a GliaSite RTS (a recently FDA-approved balloon catheter system for intracranial intracavitary brachytherapy) was inserted into the surgical cavity. Over four days a radiation dose of 152 Gy was delivered at the balloon surface dose and 50.0Gy was delivered at a depth of 7 mm from balloon surface. The patient received subsequent treatment with external beam radiation and chemotherapy. The patient tolerated her treatment well and has shown no evidence of tumor recurrence with a follow up of 18 months. CONCLUSIONS: Boost intracavitary brachytherapy can play a critical role in preventing local recurrence and early death in patients with primary brain sarcomas.