SCA7

SCA7, or spinocerebellar ataxia type 7, is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the ATXN7 gene. The abnormal expansion leads to an altered ataxin-7 protein with an expanded polyglutamine tract, contributing to progressive neuron loss, particularly in the cerebellum and brainstem, and in the retina.

Clinical features typically begin with progressive gait and limb ataxia, impaired balance, dysarthria, and nystagmus. A hallmark of SCA7 is retinal degeneration, often presenting as cone-rod dystrophy that causes progressive visual impairment and photophobia, with central vision loss in many patients. The age of onset is variable, usually from adolescence to adulthood, and disease progression tends to be gradual but relentless. Anticipation can occur, with more severe or earlier-onset disease in subsequent generations as repeat length increases.

Inheritance is autosomal dominant, so a single pathogenic ATXN7 allele is sufficient to cause disease. The pathogenic mechanism involves toxic effects of the polyglutamine-expanded ataxin-7 protein, leading to degeneration of cerebellar circuits and retinal cells.

Diagnosis is established by genetic testing showing an expanded ATXN7 CAG repeat. Neuroimaging may reveal cerebellar atrophy, and ophthalmologic evaluation can document cone-rod dystrophy. The differential includes other spinocerebellar ataxias and neurodegenerative retinal diseases.

There is no cure. Management is multidisciplinary and supportive, emphasizing physical, occupational, and speech therapy, rehabilitation, vision rehabilitation, and genetic counseling. Treatment aims to alleviate symptoms, maximize function, and address complications, while monitoring for disease progression and associated manifestations.