An unusual presentation of Huntington’s disease-like syndrome in a patient with Xeroderma pigmentosum type F: Case report and review of the literature

Abstract

Background

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.

Case

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 ERCC4 gene, confirming XP-F diagnosis.

Literature review

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.

Conclusion

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.