Introne Wendy J, Westbroek Wendy, Groden Catherine A, Bhambhani Vikas, Golas Gretchen A, Baker Eva H, Lehky Tanya J, Snow Joseph, Ziegler Shira G, Malicdan May Christine V, Adams David R, Dorward Heidi M, Hess Richard A, Huizing Marjan, Gahl William A, Toro Camilo
From the Office of the Clinical Director (W.J.I., C.A.G., V.B., G.A.G., W.A.G., C.T.) and Human Biochemical Genetics Section, Medical Genetics Branch (W.W., S.G.Z., M.C.V.M. D.R.A., H.M.D., R.A.H., M.H., W.A.G.), National Human Genome Research Institute, Department of Radiology and Imaging Sciences, Clinical Center (E.H.B.), Electromyography Section, Office of the Clinical Director, National Institute of Neurological Disorders and Stroke (T.J.L.), and Office of the Clinical Director, National Institute of Mental Health (J.S.), National Institutes of Health, Bethesda, MD; and Metabolic and Clinical Geneticist (V.B.), Department of Medical Genetics, Children's Hospitals and Clinics of Minnesota, Minneapolis.
Neurology. 2017 Feb 14;88(7):e57-e65. doi: 10.1212/WNL.0000000000003622.
To delineate the developmental and progressive neurodegenerative features in 9 young adults with the atypical form of Chediak-Higashi disease (CHD) enrolled in a natural history study.
Patients with atypical clinical features, but diagnostically confirmed CHD by standard evaluation of blood smears and molecular genotyping, underwent complete neurologic evaluation, MRI of the brain, electrophysiologic examination, and neuropsychological testing. Fibroblasts were collected to investigate the cellular phenotype and correlation with the clinical presentation.
In 9 mildly affected patients with CHD, we documented learning and behavioral difficulties along with developmental structural abnormalities of the cerebellum and posterior fossa, which are apparent early in childhood. A range of progressive neurologic problems emerge in early adulthood, including cerebellar deficits, polyneuropathies, spasticity, cognitive decline, and parkinsonism.
Patients with undiagnosed atypical CHD manifesting some of these wide-ranging yet nonspecific neurologic complaints may reside in general and specialty neurology clinics. The absence of the typical bleeding or infectious diathesis in mildly affected patients with CHD renders them difficult to diagnose. Identification of these individuals is important not only for close surveillance of potential CHD-related systemic complications but also for a full understanding of the natural history of CHD and the potential role of the disease-causing protein, LYST, to the pathophysiology of other neurodevelopmental and neurodegenerative disorders.
在一项自然史研究中，描绘9例患有非典型形式的切-希二氏病（CHD）的年轻成年人的发育和进行性神经退行性特征。
具有非典型临床特征，但通过血液涂片标准评估和分子基因分型确诊为CHD的患者，接受了全面的神经学评估、脑部MRI、电生理检查和神经心理学测试。收集成纤维细胞以研究细胞表型及其与临床表现的相关性。
在9例轻度受影响的CHD患者中，我们记录到学习和行为困难，以及小脑和后颅窝的发育结构异常，这些在儿童早期就很明显。一系列进行性神经问题在成年早期出现，包括小脑功能缺陷、多发性神经病、痉挛、认知衰退和帕金森综合征。
表现出这些广泛但非特异性神经症状的未确诊非典型CHD患者可能就诊于普通和专科神经科门诊。轻度受影响的CHD患者缺乏典型的出血或感染素质，这使得他们难以诊断。识别这些个体不仅对于密切监测潜在的CHD相关全身并发症很重要，而且对于全面了解CHD的自然史以及致病蛋白LYST在其他神经发育和神经退行性疾病病理生理学中的潜在作用也很重要。
