Case reportThe SCA17 phenotype can include features of MSA-C, PSP and cognitive impairment
Introduction
Expanded cytosine–adenine–guanine (CAG) trinucleotide repeats have been identified as the causative mutations in disorders including spinocerebellar ataxia (SCA)-1, -2, -3, -6, -7, Huntington's disease, spinal and bulbar muscular atrophy, and dentatorubral pallidoluysian atrophy (DRPLA) [1]. Additionally, an expanded CAG repeat within the TATA box-binding protein (TBP) gene has been recently described as causing a disorder manifested with ataxia, dementia, extrapyramidal syndrome, and psychiatric symptoms [2]. This gene, located at 6q27, contains a mixed CAG/CAA repeat encoding a polyglutamine tract. This locus has been registered as SCA17.
Initially, this disorder was described in an apparently sporadic childhood-onset case in Japan [2]. Subsequently, several families with autosomal dominant inheritance were described [3], [4], [5], [6]. Here we report a SCA17 case with a phenotype not previously reported, which consisted of progressive ataxia, autonomic dysfunction, parkinsonism, supranuclear palsy and mild cognitive impairment. This mimics the multiple system atrophy-cerebellar type (MSA-C), with the unusual additional features of eye movements and cognitive abnormalities. Clinicians evaluating patients with movement disorders such as MSA-C should consider SCA17 in the differential diagnosis, especially if unusual additional features occur as well.
Section snippets
Case report
This study was performed under an IRB approved protocol, and written informed consent was obtained for genetic evaluation.
This right-handed 49-year-old ethnic Chinese male was first seen in our Neurology Department in 2001 with slowly progressive clumsiness of the limbs, dysarthria, dysphagia, gait disturbance and urination problems. According to his wife, symptoms had started with loss of dexterity in both hands, followed by unsteady gait. His pronunciation became slurred with irregular pitch
Discussion
This subject had an abnormal CAG expansion in the TBP encoding gene (under 42 repeats are considered normal in Caucasian and Japanese populations) [3], [4]. An expanded allele with 43–48 CAG/CAA repeats might be considered as intermediate alleles with reduced penetrance [6], [9]. The distribution of SCA17 in ethic Chinese in Taiwan has been reported by Wu [8]. In their study, CAG repeats in the TBP gene varied from 30 to 43 in the control group. Besides, a case with an expanded allele (46
Acknowledgment
We thank Ren-Shyan Liu for performing 18F-6-fluorodopa PET study for this patient at Taipei Veterans General Hospital.
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2022, Journal of the Neurological SciencesCitation Excerpt :Besides cerebellar ataxia, cognitive impairment, psychiatric symptoms, epileptic seizures, and hyperkinetic movements are part of the clinical picture, and thereby it is considered a Huntington's disease-like (HDL) syndrome (HDL-4). However, a hypokinetic-rigid phenotype accompanying cerebellar signs can be present [11], typically in patients with lower CAG repeats, with or without CAA interruptions [12]. Like SCA17, Dentatorubral–pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disease caused by CAG repeat expansion and is included in both SCAs and HDL syndromes due to its diverse motor phenotypes, where parkinsonian features are rarely encountered [13].
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2019, International Review of NeurobiologyCitation Excerpt :Lower range repeat expansions are correlated with clinical picture and indeed with the parkinsonian phenotype which presents later in life, as in SCA2 (Degardin et al., 2012; Riess et al., 2008; Schols et al., 2000). The clinical picture comprises cerebellar ataxia, atypical parkinsonism, autonomic dysfunction (up to 45%) and mild cognitive dysfunction (Kim et al., 2009; Lin, Wu, Lee-Chen, Shan, & Gwinn-Hardy, 2007; van Gaalen, Giunti, & van de Warrenburg, 2011) and can therefore be misdiagnosed can as MSA (Koyama, Asahina, Honma, Arai, & Hattori, 2009; Takazaki, D'Abreu, Nucci, Lopes-Cendes, & Franca, 2013). When ophthalmoplegia and peripheral neuropathy are present, may help to suspect a SCA rather than MSA (Riess et al., 2008).
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2018, Handbook of Clinical NeurologyCitation Excerpt :SCA14 phenotype may result from a gain of function rather than haploinsufficiency as no chain-terminating pathogenic variants have been found, and pathogenesis may involve altered phosphorylation-dependent pathways (Moreira et al., 2001; Asai et al., 2009). SCA17 is characterized by an extremely variable phenotype, including ataxia (95%), dementia (90%), involuntary movements (70%, chorea and dystonia, blepharospasm, torticollis, writer's cramp, foot dystonia), psychiatric symptoms, pyramidal signs, parkinsonism, and multiple system atrophy-like symptoms (Cellini et al., 2001; Lin et al., 2007). The AO ranges from 3 to 75 years (mean: 34.6 years) (Maltecca et al., 2003; Stevanin and Brice, 2008).