Objective: Highlight the complex differential diagnosis of ataxia in a patient with cutaneous lesions.

Background: Cerebellar ataxias may accompany neurocutaneous syndromes. XP is a rare genetic disease associated with cutaneous photosensitivity and increased tumor susceptibility, which may also present with neurological manifestations.

Method: Description of a progressive cerebellar ataxia with cutaneous photosensitivity.

Results: Man, 43 years-old, referenced to Neurology due to a predominantly cerebellar ataxia of insidious onset since the age of 22. Later on, he developed ophthalmoparesis, flaccid paralysis, mainly distal and lower limbs’ muscular atrophy, hyporreflexia and sensory loss (superficial and deep). He also had cutaneous photosensitivity since childhood, with generalized erythematous and scaly lesions, hyperpigmentation and blisters, mostly in exposed skin areas. There was no family history or consanguinity. Brain MRI identified diffuse cerebral, cerebellar, medulla and cervical and throracic spinal atrophy. EMG disclosed sensory-motor axonal polyneuropathy. Of laboratory investigation, there was a low vitamin E level, but the patient maintained clinical worsening under replacement therapy. Recessive (FA, vitamin E deficiency, AOA1, AOA2) and dominant (SCA1-3, SCA6-7, SCA10, SCA12, SCA17, DRPLA) ataxia genetic testing was negative. The clinical suspicion of XP was supported by a positive sister chromatid exchange test in UV-exposed lymphocytes, translating chromosomal instability, by the identification of a homozygous c.172G>A (Gly58Ser) variant in the XPA gene, of unknown significance, and by the documentation of DNA repair errors in UV-exposed fibroblast cultures of skin biopsies. Both parents were carriers of this variant.

Conclusion: XP is an autosomal recessive disorder associated with DNA repair errors. We present a rare form of ataxia that should be considered in the differential diagnosis of cerebellar ataxias, including those associated with neurocutaneous syndromes with photosensitivity, and other syndromes of DNA repair defects.

References: 1) Spivak G, Hanawalt PC. Photosensitive Human Syndromes. Mutat Res.2015;776:24–30. 2) McKinnon PJ. DNA Repair Deficiency and Neurological Disease. Nat Rev Neurosci.2009;10(2):100–112. 3) Beaudin M, Klein CJ, Rouleau GA, Dupré N. Systematic review of autosomal recessive ataxias and proposal for a classification. Cerebellum Ataxias.2017;23:4:3. 4) Abeti R, Zeitberger A, Peelo C, et al. Xeroderma pigmentosum: overview of pharmacology and novel therapeutic strategies for neurological symptoms. Br J Pharmacol. 2018, doi: 10.1111/bph.14557. 5) Black JO. Xeroderma Pigmentosum. Head and Neck Pathol 2016;10:139–144.

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