The portal for rare diseases and orphan drugs

Spinocerebellar ataxia type 11 (SCA11) prevalence is unknown but SCA11 is thought to account for 2% of ADCA type III cases. More than sixty clinically affected members from six families (of British, Pakistani, Danish, Chinese, German and French descent) have been reported to date.

SCA11 presents between the ages of 11-70 years with a mean age of onset of 25 years. It presents with the cerebellar signs such as dysarthria and progressive ataxia, eventually leading to difficulty walking and loss of balance as well as eye movement abnormalities (jerky pursuit, horizontal and vertical nystagmus and ophthalmoplegia). Pyramidal signs such as hyperreflexia mainly in the lower limbs, with positive Babinski sign are occasionally present. Rarely, dystonia and peripheral neuropathy have been reported. The disease is slowly progressive with dysphagia occurring later in the disease course. Patients usually become wheelchair bound 16 years after the onset of disease symptoms.

SCA11 is due to mutations in the tau tubulin kinase 2 TTBK2 gene (15q15.2). This gene encodes TTBK2, which is found throughout the brain, and that is essential in stabilizing Purkinje cells and phosphorylating tau protein.

Diagnosis is based on the clinical findings of pure cerebellar ataxia as well as molecular findings. Head magnetic resonance imaging (MRI) usually demonstrates the presence of cerebellar atrophy and is helpful in excluding other causes of ataxia. Molecular genetic testing identifies a mutation in the TTBK2 gene, confirming a diagnosis of SCA11.

Differential diagnoses include other forms of ADCA type III, in particular SCA5, SCA6, SCA26, SCA30 and SCA31.

Antenatal diagnosis is possible in families with a known disease causing mutation.

SCA11 is inherited autosomal dominantly and genetic counseling is possible. The disease shows full penetrance. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 50% risk of passing the mutation to offspring.

There is no cure for SCA11 and treatment is supportive. Language and speech therapy can help patients with dysarthria. Physiotherapy and the use of canes, walkers and wheelchairs can help patients remain mobile. Consultation with an ophthalmologist is recommended and prism glasses can help those with nystagmus. Neurological follow-up is recommended to monitor the progression of ataxia.

The prognosis is fair since the disease progresses very slowly (with disease duration of up to 20 years) and usually does not decrease life expectancy. Quality of life, however, is greatly affected.