Spinocerebellar ataxia type 2 (SCA2) presenting with ophthalmoplegia and developmental delay in infancy

Abstract

An 11-year-old boy was evaluated for progressive ataxia, cognitive deterioration, and ophthalmoplegia. The child initially presented with abnormal eye movements at the age of 2 months and was noted to have developmental delay at 6 months. At the age of 7 years, he developed ataxia and cognitive impairment, and subsequently manifested dysphagia and incontinence. The pertinent family history included gait difficulty in the paternal grandmother. At the age of 11, his general physical examination was normal. On neurological examination, he had bilateral external ophthalmoplegia, ataxic dysarthria, dysmetria and tremor in the upper extremities, and marked gait ataxia. An ophthalmological evaluation showed no evidence of pigmentary retinopathy. Brain MRI demonstrated cerebellar, brainstem, and cerebral atrophy. An ataxia panel showed 62 repeats in one allele of the SCA2 gene. Most cases of spinocerebellar ataxia type 2 (SCA2) present between 20 years and 40 years, and affected individuals typically have between 34 and 57 CAG repeats. Neonatal cases of SCA2 have been reported in individuals with over 200 CAG repeats. Childhood SCA2 has been reported previously in two patients but not described clinically. This case broadens the spectrum of the clinical features of infantile-onset SCA2 and highlights the importance of considering this diagnosis in infants and children.

Cognitive Impairment in Spinocerebellar Degeneration

“…Several clinical investigations disclosed the frequency of dementia in SCA2 patients to be between 19 and 42% [10,16,17,18], although in a comparison of various SCAs, Bürk et al [12] did not find significantly lower scores on neuropsychological tests in SCA2 patients. It has been reported that SCA2 patients have various cognitive disorders, such as developmental delay [19] and olfactory impairment [20]. In another study, Bürk et al [21] systematically addressed the issue of cognitive function in genetically confirmed SCA2 by means of comprehensive neuropsychological testing.…”

Spinocerebellar ataxia type 2 (SCA2) in an Egyptian family presenting with polyphagia and marked CAG expansion in infancy

“…He presented with progressive extrapyramidal manifestations, slow eye saccades and cognitive impairment. To our knowledge, our proband is the second case after the report of Moretti et al [13] with infantile onset SCA2 and intermediate CAG repeats expansion. Moreover, the unique presentations of polyphagia and obesity at the mid phase of the disease in this family highlight the previous report on the putative contribution of ataxin 2 protein in the development of obesity [10].…”

“…Further, infantile and childhood onset SCA2 were assigned in three patients; 64 and 57 repeats were reported in two cases with onset of neurological symptoms at 6 and 8 years old, respectively [3,15]. The third patient had 62 CAG repeats and manifested with abnormal eye movements at the age of 2 months associated with non-specific developmental delay while ataxia and cognitive impairment appeared at 7 years of age [13].…”

Comparative multiplex dosage analysis in spinocerebellar ataxia type 2 patients

“…Interestingly, there is an inverse correlation between the number of repeats, in the pathological range, and the age of onset of the disease (Schols et al, 1997). Specifically, larger expansions (from 130 to more than 200 CAG repeats) are detected in rare patients with the infantile and juvenile forms of SCA2 (Babovic-Vuksanovic et al, 1998;Mao et al, 2002;Moretti et al, 2004), whereas the more common smaller expansions (between 34 and 57 CAG repeats) are detected in patients with the late-onset forms of the disease appearing in adult life, by the age of about 20-40 years (Moretti et al, 2004). As it is expected for a dynamic mutation, the larger expansions of CAG repeats seen in the early forms of SCA2 originate as aberrant gametogenesis events occurring in one of the two parents bearing a repeat number in the ATXN2 gene typical of the late-onset forms (Mao et al, 2002).…”