Kufor-Rakeb Syndrome: Recognising a Rare Genetic Cause of Early-Onset Parkinsonism

Abstract

Background: Kufor–Rakeb syndrome (KRS) is a rare inherited neurodegenerative disorder caused by pathogenic variants in the ATP13A2 gene. It is characterised by juvenile-onset parkinsonism with progressive cognitive, neuropsychiatric, pyramidal, and bulbar manifestations. Case Presentation: A 22-year-old boy presented with approximately 2.5 years of progressive cognitive and behavioural decline, followed by bulbar dysfunction and motor impairment. Symptoms began at 19.5 years of age with cognitive and behavioural changes; speech impairment and dysphagia developed during the subsequent months, and motor difficulties became prominent approximately one year after symptom onset. Neurological examination demonstrated cognitive impairment, hypomimia, generalised rigidity, dysarthria, brisk lower-limb deep tendon reflexes, and bilateral extensor plantar responses. Routine laboratory investigations and targeted metabolic and disease-specific evaluations were unrevealing. Clinical exome sequencing identified a homozygous pathogenic variant in the ATP13A2 gene, c.2629G>A (p.Gly877Arg), confirming KRS. Conclusion: KRS should be considered in adolescents with progressive cognitive decline and juvenile-onset parkinsonism, particularly when routine investigations are non-diagnostic. Genetic testing is central to diagnosis and enables genetic counselling and multidisciplinary supportive care.