Objective: To present a case of late onset neurologic symptoms of ataxia, myoclonus, and cognitive impairment in a 37-year-old man with xeroderma pigmentosum (XP).

Background: XP is a rare autosomal recessive disorder of DNA excision repair characterized by photosensitivity and increased risk of UV radiation-induced skin cancer. About 25% of individuals have neurologic symptoms including sensorineural hearing loss, cognitive impairment, ataxia, and neuropathy. These symptoms may present before significant dermatologic manifestations. Patients with XP with neurologic symptoms typically have an earlier age of death compared to those without (median 29 vs. 37 years). Mutations in 9 genes can cause XP, but not all are associated with neurologic symptoms. Imaging demonstrates cortical and cerebellar atrophy.

Method: A retrospective chart review characterized the presenting neurologic symptoms and outcomes of a patient with XP. Genetic testing included known XP genes (XP panel, Prevention Genetics).

Results: A 37-year-old man presented with ataxia, dysarthria, and falls. He had been diagnosed with XP at age 3 months after a severe skin burn; genetic testing had not been performed. He subsequently developed cognitive decline with significant memory impairment at age 38. He had no family history of photosensitivity, ataxia, or cognitive decline. His neurologic examination demonstrated cognitive impairment (MoCA 12/30) and diffuse cerebellar findings including hypermetric saccades, dysarthria, and appendicular and gait ataxia. He subsequently developed diffuse intermittent myoclonus with superimposed choreoathetoid movements. Prior laboratory work-up (vitamin E level, paraneoplastic panel, etc.) was unrevealing. MRI brain at age 36 demonstrated cerebral and cerebellar atrophy. Initial genetic testing (Athena Comprehensive Ataxia Panel) was negative for a pathogenic mutation. Sequencing of known XP genes revealed two heterozygous pathogenic mutations in the XPA gene (c.555G>C/c.722_785del), confirming his diagnosis of XP.

Conclusion: Mutations in the XPA gene are known to cause XP with neurologic abnormalities, as in our patient. Therefore, XP should be considered in patients (both children and younger adults) with chorea, ataxia, or myoclonus and a history of photosensitivity. Treatment of neurologic symptoms associated with XP are purely supportive and symptomatic.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/late-onset-ataxia-myoclonus-and-cognitive-decline-in-a-patient-with-xeroderma-pigmentosum-a-case-report/