Waung Maggie W, Ma Fion, Wheeler Allison G, Zai Clement C, So Joyce
Division of General Neurology, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA.
Institute for Human Genetics, University of California San Francisco School of Medicine, San Francisco, CA 94143, USA.
Biology (Basel). 2023 Nov 22;12(12):1459. doi: 10.3390/biology12121459.
Neurogenetic diseases affect individuals across the lifespan, but accurate diagnosis remains elusive for many patients. Adults with neurogenetic disorders often undergo a long diagnostic odyssey, with multiple specialist evaluations and countless investigations without a satisfactory diagnostic outcome. Reasons for these diagnostic challenges include: (1) clinical features of neurogenetic syndromes are diverse and under-recognized, particularly those of adult-onset, (2) neurogenetic syndromes may manifest with symptoms that span multiple neurological and medical subspecialties, and (3) a positive family history may not be present or readily apparent. Furthermore, there is a large gap in the understanding of how to apply genetic diagnostic tools in adult patients, as most of the published literature focuses on the pediatric population. Despite these challenges, accurate genetic diagnosis is imperative to provide affected individuals and their families guidance on prognosis, recurrence risk, and, for an increasing number of disorders, offer targeted treatment. Here, we provide a framework for recognizing adult neurogenetic syndromes, describe the current diagnostic approach, and highlight studies using next-generation sequencing in different neurological disease cohorts. We also discuss diagnostic pitfalls, barriers to achieving a definitive diagnosis, and emerging technology that may increase the diagnostic yield of testing.
神经遗传疾病影响着各个年龄段的个体，但对许多患者来说，准确诊断仍然难以实现。患有神经遗传疾病的成年人往往要经历漫长的诊断过程，接受多次专科评估和无数项检查，却得不到令人满意的诊断结果。这些诊断难题的原因包括：（1）神经遗传综合征的临床特征多种多样且未得到充分认识，尤其是成人发病型；（2）神经遗传综合征可能表现出跨越多个神经科和医学亚专科的症状；（3）可能没有阳性家族史或家族史不明显。此外，在如何将基因诊断工具应用于成年患者方面，人们的认识存在很大差距，因为大多数已发表的文献都集中在儿科人群。尽管存在这些挑战，但准确的基因诊断对于为受影响的个体及其家庭提供预后、复发风险指导以及针对越来越多的疾病提供靶向治疗至关重要。在此，我们提供一个识别成人神经遗传综合征的框架，描述当前的诊断方法，并强调在不同神经疾病队列中使用下一代测序的研究。我们还将讨论诊断陷阱、实现明确诊断的障碍以及可能提高检测诊断率的新兴技术。
