Mutation in RNF170 Causes Unsteady Gait with Hypertrophic Olivary Degeneration

RNF170基因突变导致步态不稳和橄榄核肥大性退化

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Abstract

Hypertrophic olivary degeneration (HOD) is a rare form of transsynaptic degeneration resulting from disruption of the Guillain-Mollaret triangle, typically presenting with palatal tremor, ataxia, and nystagmus. Mutations in the Ring Finger Protein 170 (RNF170) gene have been associated with autosomal dominant sensory ataxia. However, the coexistence of HOD and an RNF170 mutation has rarely been reported. A 60-year-old female presented with progressive gait instability, vertigo, oscillopsia, and a sensation of walking on cotton. Neurological examination revealed pendular nystagmus, slow rhythmic palatal myoclonus, broad-based gait, positive Romberg sign, and clumsy tandem gait. Cognitive function was intact. Magnetic resonance imaging showed bilateral hypertrophy of the inferior olivary nuclei with T2 hyperintensity, consistent with HOD, along with mild right cerebellar atrophy. No brainstem infarction, hemorrhage, or demyelinating lesions were identified. Genetic testing revealed a heterozygous mutation in the RNF170 gene. There was no family history of ataxia, and screening for common spinocerebellar ataxia genes was negative. This case describes an unusual presentation of HOD without an identifiable secondary structural lesion, occurring in a patient with an RNF170 mutation. The findings suggest that RNF170-related neurodegeneration may predispose to or mimic HOD. In patients with unexplained HOD and prominent ataxia, screening for RNF170 gene mutations should be considered.

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