皮膚生検が診断に有用であった非典型CADASILの1例

Skin Biopsy is a Useful Tool for the Diagnosis of Atypical CADASIL: A Case Report

患者は57歳の男性。片頭痛とうつ病の既往あり。最近，仕事での誤りが多くなり精査のため入院した。神経心理検査で遂行機能障害があり，頭部MRIでは大脳白質病変が認められた。家族歴はないが精査のため皮膚生検を施行し，オスミウム好性顆粒状物質（granular osmiophilic material：GOM）が陽性であることからCADASILと診断した。NOTCH3遺伝子検査ではexon 8で本邦では初めてのR427C変異を認めた。皮膚生検は簡便で非典型例CADASILの診断および稀な遺伝子変異の発見に有用と考えられた。

Abstract

A 57-year-old man developed migraine at the age of 25 years. Thereafter, he developed depression at the age of 50 years, and was admitted to a psychiatric hospital at the age of 54 years because of deteriorating depression. He returned to his work after receiving treatment for depression; however, he made mistakes several times in his work. He was referred to our hospital for further neurological evaluation. The results of the neurological examination performed on admission were unremarkable. His Mini Mental State Examination (MMSE) score was 24/30, and neuropsycological evaluations revealed executive dysfunction. There was no family history of dementia or cerebral infarction. Magnetic resonance fluid attenuated inversion recovery (MR FLAIR) image of the brain showed hyperintense lesions around the lateral ventricle without involvement in the temporal pole and external capsule. Despite a lack of family history of dementia and cerebral infarction and non-specific brain MRI findings, his history of headache and depression were suggestive of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Therefore, skin biopsy was performed; electron microscopy of the biopsied sample revealed granular osmiophilic material deposits. Genetic analysis of the NOTCH3 gene showed a missense mutation with substitution of R427C in exon 8, i.e., out of the hot-spot, exon 3, and 4. Thus, skin biopsy is a useful tool for diagnosing atypical CADASIL.

(Received July 7, 2015; Accepted August 6, 2015; Published December 1, 2015)