RESUMO
OBJECTIVE: Reporting a novel mutation in the HTRA1 gene in a CARASIL patient from Americas. METHODS: Clinical presentation and neuroimaging were consistent with CARASIL. HTRA1 DNA sequencing was performed using advanced ("next generation") sequencing technology. The results revealed a homozygous missense mutation as c.616G>A (p.Gly206Arg) in the HTRA1 gene. RESULTS: A 24-year-old man with a history of chronic back pain presented with recurrent ischemic strokes. A diagnosis of CARASIL was made with the finding of a novel homozygous missense mutation c.616G>A in HTRA1 gene, resulting in change from Glycine to Arginine in the Serine Protease HTRA1. Brain imaging showed multiple lacunar infarcts with extensive abnormalities of the white matter that spared the external capsules. He also had unilateral decreased hearing with craniofacial asymmetry. None of the above features have been previously described in known CARASIL patients. Both parents of the proband were heterozygous for the same missense mutation. CONCLUSION: We discovered a novel missense mutation (c.616G>A) associated with a phenotype of CARASIL. This is the first genetically backed case of CARASIL in the new world. The patient's craniofacial abnormalities, including asymmetry of the head, may be related to impaired modulation of transforming growth factor-ß1, the result of loss of proteolytic activity of HTRA1. External capsules remained unaffected, despite findings of advanced changes in the rest of the cerebral white matter. Literature is briefly reviewed. The patient's history, neurological exam, neuroimaging, and genetic testing are included.
Assuntos
Alopecia/genética , Infarto Cerebral/genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Leucoencefalopatias/genética , Mutação de Sentido Incorreto , Doenças da Coluna Vertebral/genética , Alopecia/complicações , Alopecia/diagnóstico , Alopecia/fisiopatologia , Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico , Infarto Cerebral/fisiopatologia , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/genética , Análise Mutacional de DNA , Imagem de Difusão por Ressonância Magnética , Predisposição Genética para Doença , Perda Auditiva Unilateral/diagnóstico , Perda Auditiva Unilateral/genética , Homozigoto , Humanos , Leucoencefalopatias/complicações , Leucoencefalopatias/diagnóstico , Leucoencefalopatias/fisiopatologia , Masculino , Neuroimagem/métodos , Exame Neurológico , New Jersey , Fenótipo , Doenças da Coluna Vertebral/complicações , Doenças da Coluna Vertebral/diagnóstico , Doenças da Coluna Vertebral/fisiopatologia , Acidente Vascular Cerebral Lacunar/diagnóstico , Acidente Vascular Cerebral Lacunar/genética , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Cerebral venous sinus thrombosis (CVST) can have devastating results, with mortality reported in 44% of cases. No randomized trials exist in order to define what qualifies as failure of conservative therapy, and there is no specific intervention to date which is considered safe and effective. Case series suggest that thrombolysis infusion is safer than thrombectomy, but methods of administration, dose, and duration of therapy tend to vary widely. We present three consecutive CVST patients treated with heparin who suffered both clinical and radiographic deterioration, and went on to have endovascular therapy. Each patient was successfully recanalized by placing a 0.027-inch microcatheter at the proximal portion of the thrombus and infusing 20 mg of alteplase dissolved in 1 liter of normal saline infused at 100 ml per hour for an infusion of 2 mg of alteplase per hour for ten hours.
