Cleene Nicolas De, Carbone Federico, Cerejo Clancy, Peball Marina, Stanzial Franco, Benedicenti Francesco, Lunzer Renate, Seppi Klaus, Heim Beatrice
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Genetic Counseling Service, Department of Pediatrics, Regional Hospital of Bolzano, Bolzano, Italy.
Clin Park Relat Disord. 2025 May 9;12:100340. doi: 10.1016/j.prdoa.2025.100340. eCollection 2025.
Xeroderma pigmentosum (XP) is a rare genetic disease in which the Nucleotide Excision Repair (NER) system is affected, resulting in defective DNA-repair. Clinical features are UV-light hypersensitivity with erythema, corneal lesions, and increased risk for skin cancers. Around 20% of affected individuals develop neurological manifestations like movement disorders due to neurodegeneration.
We report a 33-year-old man, presenting with mild choreatic movements of the lower face and limbs, executive dysfunction and mild atactic features. Dermatological changes were seen on sun-exposed skin. Brain MRI revealed global atrophy. Whole exome sequencing and familial segregation analysis revealed two compound heterozygous mutations in the gene, confirming XP-F diagnosis.
An extensive literature review identified sixteen studies reporting patients with confirmed XP as well as chorea as extrapyramidal movement disorder in their clinical phenotype. The clinical phenotyping of these patients was carefully evaluated, listed and analysed. In addition, available genetic data was systematically collected and reviewed.
We describe an XP-patient with a Huntingtońs disease (HD)-like syndrome with discrete cerebellar ataxia. Through reviewing the literature, we identified a total of 41 XP-patients with chorea. Therefore, we suggest testing of NER genes in patients with a HD-like syndrome and negative genetic testing for HD, especially when dermatological changes and atactic features are present.
着色性干皮病（XP）是一种罕见的遗传性疾病，其中核苷酸切除修复（NER）系统受到影响，导致DNA修复缺陷。临床特征为对紫外线过敏，伴有红斑、角膜病变，以及皮肤癌风险增加。约20%的患者会出现神经学表现，如因神经退行性变导致的运动障碍。
我们报告一名33岁男性，表现为面部下部和四肢轻度舞蹈样动作、执行功能障碍和轻度共济失调特征。在暴露于阳光的皮肤上可见皮肤改变。脑部MRI显示全脑萎缩。全外显子组测序和家系分离分析显示该基因存在两个复合杂合突变，确诊为XP-F型。
广泛的文献综述确定了16项研究，报告了确诊为XP且临床表型中存在舞蹈症作为锥体外系运动障碍的患者。对这些患者的临床表型进行了仔细评估、列出并分析。此外，系统收集并审查了可用的遗传数据。
我们描述了一名患有类似亨廷顿舞蹈病（HD）综合征且伴有离散性小脑共济失调的XP患者。通过文献综述，我们共确定了41例患有舞蹈症的XP患者。因此，我们建议对患有类似HD综合征且HD基因检测为阴性的患者进行NER基因检测，尤其是当存在皮肤改变和共济失调特征时。
