DentatorubralPallidoluysian

Dentatorubralpallidoluysian atrophy, commonly abbreviated DRPLA, is a rare hereditary neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the ATN1 gene on chromosome 12. The name reflects degeneration in multiple deep brain structures: the dentate nucleus of the cerebellum, the red nucleus (rubral), the globus pallidus (pallidal), and Luys’ body (nucleus of Luys, including subthalamic regions).

DRPLA is inherited in an autosomal dominant pattern with anticipation, so symptoms often become more severe or appear at younger ages in successive generations due to increasing CAG repeat length. The condition occurs worldwide but has a relatively higher reported frequency in Japanese populations. Onset ranges from childhood to adulthood, with juvenile forms typically appearing before age 20 and adult forms presenting later.

Clinical features vary by age of onset. The juvenile form commonly presents with myoclonus, seizures, ataxia, and rapid cognitive decline, while the adult form more often shows ataxia with movement abnormalities such as chorea or dystonia; seizures can be present but are less frequent. Psychiatric symptoms, motor disturbances, dysarthria, and oculomotor abnormalities may occur as the disease progresses.

Diagnosis is established by genetic testing revealing the ATN1 CAG repeat expansion. Neuroimaging, especially MRI, may show cerebellar and brainstem atrophy. Pathologically, there is degeneration and gliosis in the dentate nucleus, red nucleus, pallidum, and Luys’ body.

Management is supportive and symptomatic, as there is no disease-modifying treatment. Therapeutic approaches target seizures, movement disorders, and cognitive/functional decline, with multidisciplinary care including neurology, rehabilitation, and mental health support. The prognosis is variable and generally reflects age of onset and rate of progression, with juvenile-onset disease often progressing more rapidly.