Vol 54, No 4 (2020)
Short communication
Published online: 2020-07-20
Submitted: 2020-03-20
Accepted: 2020-06-03
Get Citation

Spinocerebellar ataxia type 6 family with phenotypic overlap with Multiple System Atrophy

Rana Hanna Al-Shaikh, Anna I. Wernick, Audrey J. Strongosky, Alexandra I. Soto-Beasley, Jay A. van Gerpen, William P. Cheshire, Ryan J. Uitti, Owen A. Ross, Zbigniew K. Wszolek
DOI: 10.5603/PJNNS.a2020.0053
·
Pubmed: 32687595
·
Neurol Neurochir Pol 2020;54(4):350-355.

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Vol 54, No 4 (2020)
Short communication
Published online: 2020-07-20
Submitted: 2020-03-20
Accepted: 2020-06-03

Abstract

Aim of the study. Multiple system atrophy (MSA) and spinocerebellar ataxia (SCA) share similar symptomatology. We describe a rare occurrence of familial MSA that proved to be SCA6 upon genetic analysis.

Materials and methods. Eighty MSA patients were enrolled in our study; blood samples were collected and genetic screening of the familial case for known SCA loci was performed.

Results. A 68-year-old woman presented with recurrent and severe episodes of light-headedness, imbalance, frequent falls, neck and lower back stiffness, subjective arm and leg weakness, and numbness and tingling in both feet. One year later, her condition had declined; she experienced more falls, worsening instability, again more generalised but still subjective weakness, impaired fine motor movements, slurred speech, difficulty swallowing, episodes of choking, bladder incontinence, and constipation. Clinical suspicion included parkinsonism, MSA, and SCA. The patient was enrolled in our MSA study and was found to have 22 and 12 CAG repeats in CACNA1A. The other 79 clinical MSA patients were negative for SCA6 screening.

Conclusions and clinical implications. While MSA and SCA may have similar presentations during early disease stages, the presence of both conditions on the list of differential diagnoses can be a diagnostic dilemma. Further analysis will aid in developing a biomarker to distinguish between the two conditions and guide proper management.

Abstract

Aim of the study. Multiple system atrophy (MSA) and spinocerebellar ataxia (SCA) share similar symptomatology. We describe a rare occurrence of familial MSA that proved to be SCA6 upon genetic analysis.

Materials and methods. Eighty MSA patients were enrolled in our study; blood samples were collected and genetic screening of the familial case for known SCA loci was performed.

Results. A 68-year-old woman presented with recurrent and severe episodes of light-headedness, imbalance, frequent falls, neck and lower back stiffness, subjective arm and leg weakness, and numbness and tingling in both feet. One year later, her condition had declined; she experienced more falls, worsening instability, again more generalised but still subjective weakness, impaired fine motor movements, slurred speech, difficulty swallowing, episodes of choking, bladder incontinence, and constipation. Clinical suspicion included parkinsonism, MSA, and SCA. The patient was enrolled in our MSA study and was found to have 22 and 12 CAG repeats in CACNA1A. The other 79 clinical MSA patients were negative for SCA6 screening.

Conclusions and clinical implications. While MSA and SCA may have similar presentations during early disease stages, the presence of both conditions on the list of differential diagnoses can be a diagnostic dilemma. Further analysis will aid in developing a biomarker to distinguish between the two conditions and guide proper management.

Get Citation

Keywords

cerebellum, gait disorders/ataxia, SCA, spinocerebellar ataxia

Supplementary Files (2)
Supplemental Figure 1. Sequential Sagittal T1 Flair Cranial Sections Using Magnetic Resonance Imaging Captured 4 Years Apart
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Supplemental Table 1. List of SCA genes screened in the familial proband
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About this article
Title

Spinocerebellar ataxia type 6 family with phenotypic overlap with Multiple System Atrophy

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 54, No 4 (2020)

Pages

350-355

Published online

2020-07-20

DOI

10.5603/PJNNS.a2020.0053

Pubmed

32687595

Bibliographic record

Neurol Neurochir Pol 2020;54(4):350-355.

Keywords

cerebellum
gait disorders/ataxia
SCA
spinocerebellar ataxia

Authors

Rana Hanna Al-Shaikh
Anna I. Wernick
Audrey J. Strongosky
Alexandra I. Soto-Beasley
Jay A. van Gerpen
William P. Cheshire
Ryan J. Uitti
Owen A. Ross
Zbigniew K. Wszolek

References (30)
  1. Ito, K., , Differentiation Between Multiple System Atrophy and Other Spinocerebellar Degenerations Using Diffusion Kurtosis Imaging. Acad Radiol, 2019. 26(11): p. : e333–e339.
  2. Hanna Al Shaikh R, Caulfield T, Strongosky AJ, et al. TRIO gene segregation in a family with cerebellar ataxia. Neurol Neurochir Pol. 2018; 52(6): 743–749.
  3. Fujioka S, Sundal C, Wszolek ZK. Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics. Orphanet J Rare Dis. 2013; 8: 14.
  4. Whaley NR, Fujioka S, Wszolek ZK. Autosomal dominant cerebellar ataxia type I: a review of the phenotypic and genotypic characteristics. Orphanet J Rare Dis. 2011; 6: 33.
  5. Casey, H.L. and C.M. Gomez, Spinocerebellar Ataxia Type 6, in GeneReviews((R)), M.P. Adam, , Editors. 1993: Seattle. (WA).
  6. Buijsen RAM, Toonen LJA, Gardiner SL, et al. Genetics, Mechanisms, and Therapeutic Progress in Polyglutamine Spinocerebellar Ataxias. Neurotherapeutics. 2019; 16(2): 263–286.
  7. Ishikawa K, Tanaka H, Saito M, et al. Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1. Am J Hum Genet. 1997; 61(2): 336–346.
  8. Shizuka M, Watanabe M, Ikeda Y, et al. Molecular analysis of a de novo mutation for spinocerebellar ataxia type 6 and (CAG)n repeat units in normal elder controls. Journal of the Neurological Sciences. 1998; 161(1): 85–87.
  9. Mariotti C, Gellera C, Grisoli M, et al. Pathogenic effect of an intermediate-size SCA-6 allele (CAG)(19) in a homozygous patient. Neurology. 2001; 57(8): 1502–1504.
  10. Yabe I, Sasaki H, Matsuura T, et al. SCA6 mutation analysis in a large cohort of the Japanese patients with late-onset pure cerebellar ataxia. Journal of the Neurological Sciences. 1998; 156(1): 89–95.
  11. Gilman S, Low PA, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. Journal of the Neurological Sciences. 1999; 163(1): 94–98.
  12. Gilman, S., , Second consensus statement on the diagnosis of multiple system atrophy. Neurology, 2008. 71(9): p. : 670–6.
  13. Lewis, P., Familial Orthostatic Hypotension. Brain, 1964. 87: p. : 719–28.
  14. Quinn N. Multiple system atrophy--the nature of the beast. J Neurol Neurosurg Psychiatry. 1989; Suppl: 78–89.
  15. Soma, H., , Heredity in multiple system atrophy. J Neurol Sci, 2006. 240(1-2): p. : 107–10.
  16. Wüllner U, Abele M, Schmitz-Huebsch T, et al. Probable multiple system atrophy in a German family. J Neurol Neurosurg Psychiatry. 2004; 75(6): 924–925.
  17. Hara K, Momose Y, Tokiguchi S, et al. Multiplex Families With Multiple System Atrophy. Archives of Neurology. 2007; 64(4): 545.
  18. Bürk K, Skalej M, Dichgans J. Pontine MRI hyperintensities ("the cross sign") are not pathognomonic for multiple system atrophy (MSA). Mov Disord. 2001; 16(3): 535.
  19. Murata Y, Yamaguchi S, Kawakami H, et al. Characteristic magnetic resonance imaging findings in Machado-Joseph disease. Arch Neurol. 1998; 55(1): 33–37.
  20. Yeh TH, Lu CS, Chou YH, et al. Autonomic Dysfunction in Machado-Joseph Disease. Archives of Neurology. 2005; 62(4): 630.
  21. Kim, M., , Differential value of brain magnetic resonance imaging in multiple system atrophy cerebellar phenotype and spinocerebellar ataxias. Sci Rep, 2019. 9(1): p. ; 17329.
  22. Wenning GK, Tison F, Shlomo Yb, et al. Multiple system atrophy: A review of 203 pathologically proven cases. Movement Disorders. 1997; 12(2): 133–147.
  23. Park H, Kim HJ, Jeon BS. Parkinsonism in spinocerebellar ataxia. Biomed Res Int. 2015; 2015: 125273.
  24. Frequency Analysis and Clinical Characterization of Spinocerebellar Ataxia Types 1, 2, 3, 6, and 7 in Korean Patients—Correction. Archives of Neurology. 2003; 60(9): 1256.
  25. Murata Y, Kawakami H, Yamaguchi S, et al. Characteristic magnetic resonance imaging findings in spinocerebellar ataxia 6. Arch Neurol. 1998; 55(10): 1348–1352.
  26. Ashizawa T, Öz G, Paulson HL. Spinocerebellar ataxias: prospects and challenges for therapy development. Nat Rev Neurol. 2018; 14(10): 590–605.
  27. Klockgether T, Lüdtke R, Kramer B, et al. The natural history of degenerative ataxia: a retrospective study in 466 patients. Brain. 1998; 121 ( Pt 4): 589–600.
  28. Li M, Ma Q, Zhao X, et al. Dilemma of multiple system atrophy and spinocerebellar ataxias. J Neurol. 2018; 265(12): 2764–2772.
  29. Massey LA, Micallef C, Paviour DC, et al. Conventional magnetic resonance imaging in confirmed progressive supranuclear palsy and multiple system atrophy. Mov Disord. 2012; 27(14): 1754–1762.
  30. Wilke C, Bender F, Hayer SN, et al. Serum neurofilament light is increased in multiple system atrophy of cerebellar type and in repeat-expansion spinocerebellar ataxias: a pilot study. J Neurol. 2018; 265(7): 1618–1624.

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