Autosomal Dominant FTH1 Variant Causing Pontocerebellar Hypoplasia and Late-Onset Neuroferritinopathy: A Case Report

常染色体显性遗传FTH1变异导致脑桥小脑发育不全和迟发性神经铁蛋白病:病例报告

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Abstract

OBJECTIVES: We report on a patient with a distinct clinical and neuroradiologic phenotype and a de novo variant in the FTH1 gene. METHODS: The patient was a 25-year-old woman with developmental delay and pontocerebellar hypoplasia, who after years of stable condition visited our hospital at age 20 years because of clinical deterioration. With consent from the patients' family, we obtained clinical, imaging, and genetic data from the patient's medical record. RESULTS: Neurologic examination demonstrated a new hypertonia, ataxia, dystonia, dysarthria, and apathy. Cerebral MRI revealed new bilateral symmetrical signal abnormalities of the basal nuclei, thalamus, cerebral peduncles, and hippocampus, indicating iron accumulation. Exome sequencing revealed a de novo monoallelic variant in the FTH1 gene, c.510_511delTC. DISCUSSION: Similar de novo FTH1 gene variants were reported in a case series of 5 patients with a similar, distinctive phenotype. Because this is a recently discovered cause of prenatal-onset cerebellar atrophy with later-onset neuroferritinopathy, our case adds to the literature to learn more about this distinct disease.

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