Clift Kristin, Guthrie Kimberly, Klee Eric W, Boczek Nicole, Cousin Margot, Blackburn Patrick, Atwal Paldeep
a Center for Individualized Medicine, Mayo Clinic , Jacksonville , FL , USA.
b Division of Biomedical Statistics and Informatics, Mayo Clinic , Rochester , MN , USA.
Prion. 2016 Nov;10(6):502-506. doi: 10.1080/19336896.2016.1254858.
Here we present a case of an asymptomatic 53-year-old woman who sought genetic testing for Familial Creutzfeldt-Jakob Disease (fCJD) after learning that her mother had fCJD. The patient's mother had a sudden onset of memory problems and rapidly deteriorating mental faculties in her late 70s, which led to difficulties ambulating, progressive non-fluent aphasia, dysphagia and death within ∼1 y of symptom onset. The cause of death was reported as "rapid onset dementia." The patient's family, unhappy with the vague diagnosis, researched prion disorders online and aggressively pursued causation and submitted frozen brain tissue from the mother to the National Prion Disease Surveillance Center, where testing revealed a previously described 5-octapeptide repeat insertion (5-OPRI) in the prion protein gene (PRNP) that is known to cause fCJD. The family had additional questions about the implications of this result and thus independently sought out genetic counseling. While rare, fCJD is likely underdiagnosed due to clinical heterogeneity, rapid onset, early non-specific symptomatology, and overlap in the differential diagnosis of Alzheimer disease and Lewy body dementias. When fCJD is identified, a multidisciplinary approach to return of results that includes the affected patient's provider, genetics professionals, and mental health professionals is key to the care of the family. We present an example case which discusses the psychosocial issues encountered and the role of genetic counseling in presymptomatic testing for incurable neurodegenerative conditions. Ordering physicians should be aware of the basic issues surrounding presymptomatic genetic testing and identify local genetic counseling resources for their patients.
在此，我们介绍一例无症状的53岁女性病例。该女性在得知其母亲患有家族性克雅氏病（fCJD）后，寻求针对fCJD的基因检测。患者的母亲在70多岁后期突然出现记忆问题，智力迅速衰退，导致行走困难、进行性非流畅性失语、吞咽困难，并在症状出现后约1年内死亡。死亡原因报告为“快速进展性痴呆”。患者家属对这一模糊诊断不满意，通过在线研究朊病毒疾病，并积极追查病因，将母亲的冷冻脑组织提交给国家朊病毒疾病监测中心，检测发现朊病毒蛋白基因（PRNP）中存在先前描述的5 - 八肽重复插入（5 - OPRI），已知该插入会导致fCJD。家属对这一结果的影响还有其他疑问，因此独立寻求了遗传咨询。虽然fCJD很罕见，但由于临床异质性、发病迅速、早期非特异性症状以及阿尔茨海默病和路易体痴呆鉴别诊断的重叠，fCJD可能未得到充分诊断。当确诊fCJD时，采用多学科方法向包括受影响患者的医疗服务提供者、遗传学专业人员和心理健康专业人员反馈检测结果，对于照顾这个家庭至关重要。我们展示了一个示例病例，讨论了所遇到的社会心理问题以及遗传咨询在不可治愈的神经退行性疾病症状前检测中的作用。开单医生应了解症状前基因检测的基本问题，并为其患者确定当地的遗传咨询资源。
