RESUMEN
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.
Asunto(s)
Cinesinas/genética , Enfermedades Mitocondriales/genética , Mioclonía/genética , Apnea/genética , Preescolar , Trastornos de Deglución/genética , Discapacidades del Desarrollo/genética , Resultado Fatal , Femenino , Mutación del Sistema de Lectura , Humanos , Lactante , Masculino , Enfermedades Mitocondriales/complicaciones , Hipotonía Muscular/genética , Mutación , Nervio Óptico/anomalíasAsunto(s)
Ojo/patología , Mucormicosis/diagnóstico , Enfermedades Orbitales/microbiología , Niño , Dacriocistitis/diagnóstico , Dacriocistitis/tratamiento farmacológico , Drenaje , Ojo/microbiología , Femenino , Humanos , Hifa/efectos de los fármacos , Hifa/crecimiento & desarrollo , Hifa/aislamiento & purificación , Mucorales/efectos de los fármacos , Mucorales/crecimiento & desarrollo , Mucorales/aislamiento & purificación , Mucormicosis/tratamiento farmacológico , Mucormicosis/microbiología , Enfermedades Orbitales/diagnóstico , Enfermedades Orbitales/diagnóstico por imagen , Enfermedades Orbitales/tratamiento farmacológico , Tomografía Computarizada por Rayos XRESUMEN
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.