Spinocerebellar ataxia type 7 (ORPHA:94147)
An autosomal dominant cerebellar ataxia type II that is characterized by progressive ataxia, motor system abnormalities, dysarthria, dysphagia and retinal degeneration leading to progressive blindness.
Epidemiology
The worldwide prevalence of the disease is estimated to be less than 1/100,000 and it is thought to account for 2-4 % of all forms of spinocerebellar ataxia (up to 7 % in Asian populations). Higher prevalence is described in some populations such as in Scandinavia or South Africa.
Clinical description
Onset of Spinocerebellar ataxia type 7 (SCA7) is generally in the second to fourth decade but can range from infancy to the sixth decade of life. Manifestations that present in infancy and early childhood include muscle weakness, wasting, hypotonia, poor feeding, failure to thrive and loss of motor milestones. Changes in visual acuity and color vision (tritanopia) may be the earliest signs of the disease, especially in younger-onset patients. In those where initial symptoms occur before adolescence, the disease progresses much faster and blindness can occur within a few years. In those with adult-onset disease, manifestations include dysmetria, poor coordination and dysdiadokinesia with progression into severe dysarthria, dysphagia and loss of motor control. Visual symptoms (hemeralopia, photophobia, abnormalities in color vision and central visual acuity) may precede, accompany or follow cerebellar ataxia in those with adult-onset SCA7 but progression is slower, with blindness occurring 10 or more years after initial symptom onset. Psychosis and cognitive decline has also been reported in some cases. Patients eventually become bedridden.
Etiology
SCA7 is due to a CAG trinucleotide repeat in the ataxin 7 (ATXN7) gene (3p21.1-p12). This mutation leads to degeneration in the cells of the retina, cerebellum and brainstem. A larger CAG-repeat expansion is associated with an earlier onset and more severe disease course.
Diagnostic methods
Diagnosis is based on characteristic clinical findings (progressive incoordination and cone-rod retinal dystrophy) as well as molecular genetic testing. A CAG trinucleotide expansion (usually 36 or more CAG repeats) in the ATXN7 gene confirms diagnosis of SCA7. Magnetic resonance imaging usually shows severe atrophy of the cerebellum and the brainstem. Electroretinogram testing reveals rod and cone abnormalities and fundoscopic examination shows macular changes later in the disease course.
Differential diagnosis
Differential diagnoses include lipid storage diseases (such as neuronal ceroid lipofuscinosis) and Leber hereditary optic neuropathy. Other forms of ADCA should also be considered but can be excluded based on the absence of retinal degeneration, which is unique to SCA7.
Antenatal diagnosis
Antenatal diagnosis is possible in families with a known ATXN7 mutation.
Genetic counseling
The disorder is inherited autosomal dominantly and genetic anticipation is observed. Genetic counseling can inform parents with the disease of the 50% risk of passing it on to their children.
Management and treatment
There is no cure for SCA7 and treatment is supportive. Activity should be maintained as much as possible with the help of canes and walkers. Motorized chairs may eventually be necessary. Speech therapy and communication devices should be offered to those with dysarthria. UV exposure should be limited and sunglasses worn in order to limit damage to the retina. Low vision aids may also be beneficial. Ophthalmological follow-up is essential to monitor visual acuity. Dysphagia must also be monitored and a feeding tube may be required in those with advanced disease, in order to lower the risk of aspiration pneumonia (most common cause of death).
Prognosis
The prognosis depends on the age of symptom onset. An earlier onset is associated with a more severe and rapidly progressive disease. Mean age when aid walking needed is about 35 years, and mean age when wheelchair needed is approximately 37 years.

                            Last update: 
                            January 2020


                            - Expert reviewer(s): 
                            Dr Shinsuke FUJIOKA  - Dr Yoshio TSUBOI  - Dr Zbigniew WSZOLEK