Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics

Abstract

Autosomal Dominant Cerebellar Ataxia (ADCA) Type III is a type of spinocerebellar ataxia (SCA) classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. The subtype SCA6 is the most common. These subtypes are associated with four causative genes and two loci. The severity of symptoms and age of onset can vary between each SCA subtype and even between families with the same subtype. SCA5 and SCA11 are caused by specific gene mutations such as missense, inframe deletions, and frameshift insertions or deletions. SCA6 is caused by trinucleotide CAG repeat expansions encoding large uninterrupted glutamine tracts. SCA31 is caused by repeat expansions that fall outside of the protein-coding region of the disease gene. Currently, there are no specific gene mutations associated with SCA26 or SCA30, though there is a confirmed locus for each subtype. This disease is mainly diagnosed via genetic testing; however, differential diagnoses include pure cerebellar ataxia and non-cerebellar features in addition to ataxia. Although not fatal, ADCA Type III may cause dysphagia and falls, which reduce the quality of life of the patients and may in turn shorten the lifespan. The therapy for ADCA Type III is supportive and includes occupational and speech modalities. There is no cure for ADCA Type III, but a number of recent studies have highlighted novel therapies, which bring hope for future curative treatments.

The autosomal dominant spinocerebellar ataxias: emerging mechanistic themes suggest pervasive Purkinje cell vulnerability

“…33–35 However, rare reports for some of these predominantly pure cerebellar ataxias have noted involvement of other systems, resulting in pyramidal symptoms, peripheral neuropathy and movement disorders. 76 Genetic loci, neuroradiological findings and causative genes with mutation type (if known) for the pure cerebellar ataxias are indicated in table 4.…”

Atxn2 Knockout and CAG42-Knock-in Cerebellum Shows Similarly Dysregulated Expression in Calcium Homeostasis Pathway

“…The main shared symptom of these neurodegenerative processes is motor incoordination (gait, stance, and limb ataxia) [2, 3]. Additionally, there are non-motor symptoms that are characteristic for SCA subgroups like dementia or macular degeneration.…”

Clinical characteristics of combined cases of spinocerebellar ataxia types 6 and 31

“…Penetrance is almost 100% in SCA6; however, it is believed to be incomplete in SCA31 (Fujioka et al, 2013). With respect to background, V-6, V-7, and V-8 were similar; they were all adept at running and ball games at junior high school, regular members of the volleyball club at high school, and married when they were in their early 20s.…”