Takazawa Takanori, Ikeda Ken, Ito Hirono, Aoyagi Joe, Nakamura Yoshikazu, Miura Ken, Iwamoto Konosuke, Kano Osamu, Kawabe Kiyokazu, Iwasaki Yasuo
Department of Neurology, Toho University Omori Medical Center, Tokyo.
Intern Med. 2010;49(4):339-42. doi: 10.2169/internalmedicine.49.2864. Epub 2010 Feb 15.
Gerstmann-Sträussler-Scheinker Syndrome (GSS) is an inherited prion disease characterized by midlife onset and slowly progression of cerebellar ataxia and dementia. We report a distinct phenotype of leg hyperreflexia in a Japanese family with GSS. A 38-year-old woman noticed unsteady gait at 33 years of age. Afterwards, dysarthria and writing difficulty were appeared. Her family history revealed that her grandfather and her mother had a clinical history of unsteadiness and mental changes. At 1 year after clinical onset, neurological examination showed cerebellar ataxia and leg hyperreflexia. At 4 years after onset, she suddenly developed insomnia and nocturnal howling. Her mental status disclosed marked disorientation, anxiety and irritability. Muscle stretch reflexes were increased in four extremities with Babinski's signs. Remarkable dysarthria and cerebellar ataxia were presented. Brain diffusion weighted imaging showed extensive hyperintensity signal areas in the cerebral cortex. A point mutation of the prion protein gene (PRNP) at codon 102 resulting in the substitution of proline by leucine (P102L) was identified. PRNP polymorphism exhibited homozygous methionine at codon 129 and homozygous glutamate at codon 219. She had verbal perseveration, somnolence and myoclonus of lower limbs, leading to akinetic mutism at 4 months after neuropsychiatric events. Phenotypic hallmark of our patient indicates leg hyperreflexia from an early disease course. This neurological sign differs from the previously reported clinical expression of Japanese and foreign patients with GSS (P102L). Thus, physicians should pay more attention to phenotypic heterogeneity in this prion disease.
格斯特曼-施特劳斯勒-谢inker综合征（GSS）是一种遗传性朊病毒病，其特征为中年发病，小脑共济失调和痴呆进展缓慢。我们报告了一个日本GSS家族中一种独特的下肢反射亢进表型。一名38岁女性在33岁时注意到步态不稳。此后，出现了构音障碍和书写困难。她的家族史显示，她的祖父和母亲有步态不稳和精神改变的临床病史。临床发病1年后，神经系统检查显示小脑共济失调和下肢反射亢进。发病4年后，她突然出现失眠和夜间嚎叫。她的精神状态显示出明显的定向障碍、焦虑和易怒。四肢肌肉牵张反射增强，伴有巴宾斯基征。出现明显的构音障碍和小脑共济失调。脑扩散加权成像显示大脑皮层广泛的高信号区。在朊病毒蛋白基因（PRNP）密码子102处发现一个点突变，导致脯氨酸被亮氨酸替代（P102L）。PRNP多态性在密码子129处表现为纯合甲硫氨酸，在密码子219处表现为纯合谷氨酸。在神经精神事件发生4个月后，她出现言语持续症、嗜睡和下肢肌阵挛，导致运动不能性缄默。我们患者的表型特征表明在疾病早期就出现下肢反射亢进。这种神经学体征不同于先前报道的日本和外国GSS（P102L）患者的临床表现。因此，医生应更加关注这种朊病毒病的表型异质性。
