Objective: To delineate the clinical presentation, exam phenomenology, brain MRI findings and to review the literature of the first reported adult-onset case of ultrarare ERCC1 mutation.

Background: At the age of 29 years, the patient was found to have five hepatocellular carcinomatous (HCC) tumors for which he underwent orthotopic liver transplant. In his early thirties, he developed cognitive impairment followed by gait instability resulting in falls. Examination was notable for restricted extraocular movements that did not correct with oculocephalics, dysarthria, staccato speech, and marked appendicular and axial ataxia.

Method: As the patient was identified in clinic as having progressive cerebellar ataxia, he was referred to genetics. He and his parents were evaluated with whole exome sequencing (WES).

Results: MRI brain showed diffuse atrophy, predominantly in cerebellum (Fig 1). Whole-exome sequencing was pertinent for known pathogenic variant homozygous mutation in excision repair cross-complementation group 1 (ERRC1) gene at p.(Arg156Trp) (CGG>TGG): c.466 C>T in exon 4.

Conclusion: This is the first reported case of adult-onset manifestation of homozygous ERCC1 mutation and confirms previously reported ataxia phenomenology. ERCC1 gene is involved in nucleotide excision repair. Since only a few cases have been reported in the literature, homozygous ERCC1 mutation appears to be crucial to fetal survival. All previously reported cases manifested symptoms as infants or adolescents and had early-life deaths, unlike this patient. Based on human and animal evidence, cerebellar degeneration appears to be a clinical main feature.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/first-report-of-ercc1-associated-adult-onset-hepatocellular-carcinoma-ataxia-and-cognitive-decline/