Variants in the ERCC4 gene as a Rare Cause of Cerebellar Ataxia with Dystonia: The First Case in Korea

Backgrounds: XFE progeroid syndrome is caused by a homozygous or compound heterozygous mutation in the ERCC4 gene encoding DNA repair endonuclease XPF. Clinical features of the disorder include increased skin sensitivity to ultraviolet light, increased risk of skin cancer, and growth defects. Rarely, mental retardation, cerebral atrophy, cerebellar ataxia, and cognitive decline have been reported. Herein, we report the first case of XFE progeroid syndrome with a novel variant.

Case report: A 50-year-old male patient presented with cerebellar ataxia and dystonia. He had generalised dystonia and cognitive impairment as a child. At the age of 41, neurological signs progressed and a brain MRI revealed severe diffuse cerebral atrophy involving the cerebellum. He spent most of his time indoors because of his photosensitivity. He had severe hyperpigmentation on the face and hands and thin wrinkled mottled skin. His ophthalmologic examination showed glaucoma. His neurological symptoms progressively worsened over time. Four years ago, he could not walk independently due to severe gait disturbance. WGS revealed ERCC4 gene variants (c.[2395CT] and c.[180_185del]), the latter of which was a novel variant leading to XFE progeroid syndrome.

Conclusions: This is the first Korean patient with ERCC4 biallelic variants and neurologic symptoms. These findings will help to broaden and understand the spectrum of clinical features of XFE progeroid syndrome.