Spinocerebellar ataxia type 6

Abstract

Spinocerebellar ataxia type 6 (SCA6) is the most recently identified mutation causing autosomal-dominant cerebellar ataxia without retinal degeneration (ADCA). The SCA6 mutation is allelic with episodic ataxia type 2 (EA-2), but the two differ clinically because of the presence of progressive, rather than episodic, ataxia in SCA6. SCA6 accounts for 12% of families with ADCA in an ethnically heterogeneous population of patients. Clinical examination, quantitative eye movement testing, and imaging data show that the brainstem is normal in most patients with SCA6, especially within the first 10 years of symptoms. Most patients show progressive ataxia from the onset, but several patients show an episodic course resembling EA-2. Thus, SCA6 mutations not only account for patients with ADCA I and ADCA III phenotypes but also for some patients presenting with episodic features that are typical for EA-2. Interestingly, a compound heterozygote for the SCA6 expansion manifested an earlier onset and more rapid course than family members with the same larger expanded allele.

A clinical and genetic study in a large cohort of patients with spinocerebellar ataxia type 6

“…We defined unsteadiness as a sense of instability, especially while walking. Therefore, the symptom would mainly reflect gait ataxia, which was also the most frequent initial symptom according to many previous reports (Geschwind et al 1997;Gomez et al 1997;Ikeuchi et al 1997;Stevanin et al 1997). The second most frequent initial symptom was vertigo or oscillopsia.…”

“…The induction of vertigo and oscillopsia by changes of the head position can also occur in SCA6 patients. However, these extracerebellar features have been reported with different frequencies (Geschwind et al 1997;Gomez et al 1997;Harada et al 1998;Sinke et al 2001;Durig et al 2002;Yabe et al 2003).…”

“…In Japan, SCA6 seems to be either the most common or second most common subtype of the SCAs (Matsumura et al 1997;Watanabe et al 1998;Sasaki et al 2000;Maruyama et al 2002), but its prevalence is lower in Western Europe and North America (Geschwind et al 1997;Scho¨ls et al 1997Scho¨ls et al , 1998Stevanin et al 1997). In contrast, other dominantly inherited pure cerebellar ataxias seem to be infrequent in Japan, including SCA5 (Holmberg et al 1995), SCA10 (Zu et al 1999), SCA11 (Worth et al 1999), SCA14 , SCA15 (Knight et al 2003), SCA16 (Miyoshi et al 2001), and SCA22 (Chung et al 2003).…”

“…The main clinical feature of SCA6 is slowly progressive cerebellar ataxia, but extracerebellar symptoms, such as pyramidal tract signs, abnormal involuntary movements, parkinsonism, hyporeflexia, intellectual impairment, and urinary incontinence, have also been reported (Geschwind et al 1997;Gomez et al 1997;Ikeuchi et al 1997;Matsumura et al 1997;Scho¨ls et al 1997;Stevanin et al 1997;Watanabe et al 1998;Yabe et al 1998). The induction of vertigo and oscillopsia by changes of the head position can also occur in SCA6 patients.…”

Downbeat positioning nystagmus is a common clinical feature despite variable phenotypes in an FHM1 family

“…Patients with the SCA6 also frequently experience episodes of vertigo and oscillopsia, and develop downbeat positioning nystagmus (DPN) [8], [12], [19], [21]. EA2 is characterized by episodes of cerebellar ataxia usually associated with migraine symptoms, interictal nystagmus, mild residual and in some cases a progressive cerebellar incoordination.…”