Medscape is available in 5 Language Editions – Choose your Edition here.


Olivopontocerebellar Atrophy Follow-up

  • Author: Christina J Azevedo, MD; Chief Editor: Selim R Benbadis, MD  more...
Updated: Nov 11, 2014


See the list below:

  • Falls are the primary complications in the early stages of olivopontocerebellar atrophy (OPCA).
  • Aspiration pneumonia is more common in later stages of OPCA.


Currently, no effective therapy is available for the neurodegenerative processes that constitute OPCA. Clinically, only supportive care can be given to patients with this progressive disease.

Contributor Information and Disclosures

Christina J Azevedo, MD Staff Physician, Department of Neurology, Dartmouth-Hitchcock Medical Center

Christina J Azevedo, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.


Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, Phi Beta Kappa

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nestor Galvez-Jimenez, MD, MSc, MHA The Pauline M Braathen Endowed Chair in Neurology, Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, International Parkinson and Movement Disorder Society

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics; Eisai; Glaxo Smith Kline; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics; Lundbeck; Sepracor; Sunovion; UCB; Upsher-Smith.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Kalpana Kari, MD; Syed T Arshad, MD; and Yash Mehndiratta, MD to the development and writing of this article.

  1. Friedreich N. Ueber degenerative atrophie der spinalen Hinterstrange. Virchow Arch Path Anat. 1863. 26:391-419.

  2. Friedreich N. Ueber degenerative atrophie der spinalen Hinterstrange. Virchow Arch Path Anat. 1863. 27:1-26.

  3. Marie P. Sur l'heredo-ataxie cerebelleuse.Clinique des maladies nerveuses. Semaine Med, Paris. 1893. 13:444-7.

  4. Marie P, Foix C, Alajouanine T. De l'atrophie cerebelleuse tardive a predominance corticale. Revue Neurologique, Paris. 1922. 38:849-85; 1082-111.

  5. Dejerine J, Thomas A. L'atrophie olivo-ponto-cerebelleuse. Nouv Icon de la Salpet. 1900. 13:330-70.

  6. Greenfield JG. The Spino-cerebellar Degenerations. Springfield, Ill: Charles C. Thomas; 1954.

  7. Harding AE. The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of the 'the Drew family of Walworth'. Brain. 1982 Mar. 105(Pt 1):1-28. [Medline].

  8. Konigsmark BW, Weiner LP. The olivopontocerebellar atrophies: a review. Medicine (Baltimore). 1970 May. 49(3):227-41. [Medline].

  9. Skre H, Berg K. Cerebellar ataxia and total albinism: a kindred suggesting pleitotropism or linkage. Clin Genet. 1974. 5(3):196-204. [Medline].

  10. Paulson H, Ammache Z. Ataxia and hereditary disorders. Neurol Clin. 2001. Aug;19(3):759-82, viii. [Medline].

  11. Gilman S, Little R, Johanns J, et al. Evolution of sporadic olivopontocerebellar atrophy into multiple system atrophy. Neurology. 2000 Aug 22. 55(4):527-32. [Medline].

  12. Jellinger KA. Neuropathological spectrum of synucleinopathies. Mov Disord. 2003 Sep. 18 Suppl 6:S2-12. [Medline].

  13. Stefanova N, Kaufmann WA, Humpel C, Poewe W, Wenning GK. Systemic proteasome inhibition triggers neurodegeneration in a transgenic mouse model expressing human a-synuclein under oligodendrocyte promoter: implications for multiple system atrophy. Acta Neuropathol. 2012 Apr 11. [Medline].

  14. Pikkarainen M, Hartikainen P, Soininen H, Alafuzoff I. Distribution and pattern of pathology in subjects with familial or sporadic late-onset cerebellar ataxia as assessed by p62/sequestosome immunohistochemistry. Cerebellum. 2011 Dec. 10(4):720-31. [Medline].

  15. Banfi S, Servadio A, Chung MY, et al. Identification and characterization of the gene causing type 1 spinocerebellar ataxia. Nat Genet. 1994 Aug. 7(4):513-20. [Medline].

  16. Burk K, Abele M, Fetter M, Dichgans J, Skalej M, Laccone F, et al. Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3. Brain. 1996 Oct. 119 ( Pt 5):1497-505. [Medline].

  17. Fickler A. Klinische und pathologisch-anatomische Beitraege zu den Erkrankungen des Kleinhirns. Dtsch Z Nervenheilk. 1911. 41:306-75.

  18. Winkler C. A case of olivo-pontine cerebellar atrophy and our conceptions of neo- and palaio-cerebellum. Schweiz Arch Neurol Psychiat. 1923. 13:684-702.

  19. Schut JW, Haymaker W. Hereditary ataxia: pathologic study of 5 cases of common ancestry. J Neuropath Clin Neurol. 1951. 1:183-213.

  20. Carter HR, Sukavajana C. Familial cerebello-olivary degeneration with late development of rigidity and dementia. Neurology. 1956 Dec. 6(12):876-84. [Medline].

  21. Illarioshkin SN, Tanaka H, Markova ED, et al. X-linked nonprogressive congenital cerebellar hypoplasia: clinical description and mapping to chromosome Xq. Ann Neurol. 1996 Jul. 40(1):75-83. [Medline].

  22. Bertini E, des Portes V, Zanni G, et al. X-linked congenital ataxia: a clinical and genetic study. Am J Med Genet. 2000 May 1. 92(1):53-6. [Medline].

  23. Chou SM, Gilbert EF, Chun RW, et al. Infantile olivopontocerebellar atrophy with spinal muscular atrophy (infantile OPCA + SMA). Clin Neuropathol. 1990 Jan-Feb. 9(1):21-32. [Medline].

  24. Barth PG. Pontocerebellar hypoplasias. An overview of a group of inherited neurodegenerative disorders with fetal onset. Brain Dev. 1993 Nov-Dec. 15(6):411-22. [Medline].

  25. Rajab A, Mochida GH, Hill A, et al. A novel form of pontocerebellar hypoplasia maps to chromosome 7q11-21. Neurology. 2003 May 27. 60(10):1664-7. [Medline].

  26. Albrecht S, Schneider MC, Belmont J, Armstrong DL. Fatal infantile encephalopathy with olivopontocerebellar hypoplasia and micrencephaly. Report of three siblings. Acta Neuropathol (Berl). 1993. 85(4):394-9. [Medline].

  27. Patel MS, Becker LE, Toi A, et al. Severe, fetal-onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5?. Am J Med Genet A. 2006 Mar 15. 140(6):594-603. [Medline].

  28. Colella S, Nardo T, Botta E, et al. Identical mutations in the CSB gene associated with either Cockayne syndrome or the DeSanctis-cacchione variant of xeroderma pigmentosum. Hum Mol Genet. 2000 May 1. 9(8):1171-5. [Medline].

  29. Kanda T, Oda M, Yonezawa M, et al. Peripheral neuropathy in xeroderma pigmentosum. Brain. 1990 Aug. 113 (Pt 4):1025-44. [Medline].

  30. De Sanctis C, Cacchione A. L'idiozia xerodermica [xerodermic idiocy]. Rivista Sperimentale di Freniatria e Medicina Legale delle Alienazioni Mentali. 1932. 56:269-92.

  31. Agamanolis DP, Potter JL, Naito HK, et al. Lipoprotein disorder, cirrhosis, and olivopontocerebellar degeneration in two siblings. Neurology. 1986 May. 36(5):674-81. [Medline].

  32. Harding BN, Dunger DB, Grant DB, Erdohazi M. Familial olivopontocerebellar atrophy with neonatal onset: a recessively inherited syndrome with systemic and biochemical abnormalities. J Neurol Neurosurg Psychiatry. 1988 Mar. 51(3):385-90. [Medline].

  33. Menzel P. Beitrage zur Kenntnis der hereditaren Ataxie und Kleinhirnatrophie. Archiv fur Psychiatrie und Nervenkrankheiten, Berlin. 1891. 22:160-90.

  34. Waggoner RW, Lowenberg K, Speicher KG. Hereditary cerebellar ataxia: report of a case and genetic study. Arch Neurol Psychiat. 1938. 39:570-86.

  35. Schut JW. Hereditary ataxia: clinical study through six generations. Arch Neurol Psychiat. 1950. 63:535-68.

  36. Orr HT, Chung MY, Banfi S, et al. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet. 1993 Jul. 4(3):221-6. [Medline].

  37. Donato SD, Mariotti C, Taroni F. Spinocerebellar ataxia type 1. Handb Clin Neurol. 2012. 103:399-421. [Medline].

  38. Boller F, Segarra JM. Spino-pontine degeneration. Eur Neurol. 1969. 2(6):356-73. [Medline].

  39. Wadia NH, Swami RK. A new form of heredo-familial spinocerebellar degeneration with slow eye movements (nine families). Brain. 1971. 94(2):359-74. [Medline].

  40. Ueyama H, Kumamoto T, Nagao S, et al. Clinical and genetic studies of spinocerebellar ataxia type 2 in Japanese kindreds. Acta Neurol Scand. 1998 Dec. 98(6):427-32. [Medline].

  41. Nakano KK, Dawson DM, Spence A. Machado disease. A hereditary ataxia in Portuguese emigrants to Massachusetts. Neurology. 1972 Jan. 22(1):49-55. [Medline].

  42. Kawaguchi Y, Okamoto T, Taniwaki M, et al. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet. 1994 Nov. 8(3):221-8. [Medline].

  43. Gardner K, Alderson K, Galster B. Autosomal dominant spinocerebellar ataxia: clinical description of a distinct hereditary ataxia and genetic localization to chromosome 16 (SCA4) in a Utah kindred. Neurology. 1994. 44:A361 only.

  44. Hellenbroich Y, Bubel S, Pawlack H, et al. Refinement of the spinocerebellar ataxia type 4 locus in a large German family and exclusion of CAG repeat expansions in this region. J Neurol. 2003 Jun. 250(6):668-71. [Medline].

  45. Ishikawa K, Toru S, Tsunemi T, et al. An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide substitution in the 5' untranslated region of the gene encoding a protein. Am J Hum Genet. 2005 Aug. 77(2):280-96. [Medline].

  46. Ikeda Y, Dick KA, Weatherspoon MR, et al. Spectrin mutations cause spinocerebellar ataxia type 5. Nat Genet. 2006 Feb. 38(2):184-90. [Medline].

  47. Subramony SH, Fratkin JD, Manyam BV, Currier RD. Dominantly inherited cerebello-olivary atrophy is not due to a mutation at the spinocerebellar ataxia-I, Machado-Joseph disease, or Dentato-Rubro-Pallido-Luysian atrophy locus. Mov Disord. 1996 Mar. 11(2):174-80. [Medline].

  48. Zhuchenko O, Bailey J, Bonnen P, et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet. 1997 Jan. 15(1):62-9. [Medline].

  49. David G, Abbas N, Stevanin G, et al. Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat Genet. 1997 Sep. 17(1):65-70. [Medline].

  50. Koob MD, Moseley ML, Schut LJ, et al. An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet. 1999 Apr. 21(4):379-84. [Medline].

  51. Ikeda Y, Shizuka M, Watanabe M, et al. Molecular and clinical analyses of spinocerebellar ataxia type 8 in Japan. Neurology. 2000 Feb 22. 54(4):950-5. [Medline].

  52. Factor SA, Qian J, Lava NS, et al. False-positive SCA8 gene test in a patient with pathologically proven multiple system atrophy. Ann Neurol. 2005 Mar. 57(3):462-3. [Medline].

  53. Grewal RP, Tayag E, Figueroa KP, et al. Clinical and genetic analysis of a distinct autosomal dominant spinocerebellar ataxia. Neurology. 1998 Nov. 51(5):1423-6. [Medline].

  54. Zu L, Figueroa KP, Grewal R, Pulst SM. Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22. Am J Hum Genet. 1999 Feb. 64(2):594-9. [Medline].

  55. Grewal RP, Achari M, Matsuura T, et al. Clinical features and ATTCT repeat expansion in spinocerebellar ataxia type 10. Arch Neurol. 2002 Aug. 59(8):1285-90. [Medline].

  56. Worth PF, Giunti P, Gardner-Thorpe C, et al. Autosomal dominant cerebellar ataxia type III: linkage in a large British family to a 7.6-cM region on chromosome 15q14-21.3. Am J Hum Genet. 1999 Aug. 65(2):420-6. [Medline].

  57. Holmes SE, O'Hearn EE, McInnis MG, Gorelick-Feldman DA, et al. Expansion of a novel CAG trinucleotide repeat in the 5' region of PPP2R2B is associated with SCA12. Nat Genet. 1999 Dec. 23(4):391-2. [Medline].

  58. Fujigasaki H, Verma IC, Camuzat A, et al. SCA12 is a rare locus for autosomal dominant cerebellar ataxia: a study of an Indian family. Ann Neurol. 2001 Jan. 49(1):117-21. [Medline].

  59. Waters MF, Minassian NA, Stevanin G, et al. Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat Genet. 2006 Apr. 38(4):447-51. [Medline].

  60. Yamashita I, Sasaki H, Yabe I, et al. A novel locus for dominant cerebellar ataxia (SCA14) maps to a 10.2-cM interval flanked by D19S206 and D19S605 on chromosome 19q13.4-qter. Ann Neurol. 2000 Aug. 48(2):156-63. [Medline].

  61. Brkanac Z, Bylenok L, Fernandez M, et al. A new dominant spinocerebellar ataxia linked to chromosome 19q13.4-qter. Arch Neurol. 2002 Aug. 59(8):1291-5. [Medline].

  62. Chen DH, Brkanac Z, Verlinde CL, et al. Missense mutations in the regulatory domain of PKC gamma: a new mechanism for dominant nonepisodic cerebellar ataxia. Am J Hum Genet. 2003 Apr. 72(4):839-49. [Medline].

  63. Yabe I, Sasaki H, Chen DH, et al. Spinocerebellar ataxia type 14 caused by a mutation in protein kinase C gamma. Arch Neurol. 2003 Dec. 60(12):1749-51. [Medline].

  64. Storey E, Gardner RJ, Knight MA, et al. A new autosomal dominant pure cerebellar ataxia. Neurology. 2001 Nov 27. 57(10):1913-5. [Medline].

  65. Knight MA, Kennerson ML, Anney RJ, et al. Spinocerebellar ataxia type 15 (sca15) maps to 3p24.2-3pter: exclusion of the ITPR1 gene, the human orthologue of an ataxic mouse mutant. Neurobiol Dis. 2003 Jul. 13(2):147-57. [Medline].

  66. Hara K, Fukushima T, Suzuki T, et al. Japanese SCA families with an unusual phenotype linked to a locus overlapping with SCA15 locus. Neurology. 2004 Feb 24. 62(4):648-51. [Medline].

  67. Miyoshi Y, Yamada T, Tanimura M, et al. A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome 8q22.1-24.1. Neurology. 2001 Jul 10. 57(1):96-100. [Medline].

  68. Nakamura K, Jeong SY, Uchihara T, et al. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet. 2001 Jul 1. 10(14):1441-8. [Medline].

  69. Rolfs A, Koeppen AH, Bauer I, et al. Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17). Ann Neurol. 2003 Sep. 54(3):367-75. [Medline].

  70. Maltecca F, Filla A, Castaldo I, et al. Intergenerational instability and marked anticipation in SCA-17. Neurology. 2003 Nov 25. 61(10):1441-3. [Medline].

  71. Brkanac Z, Fernandez M, Matsushita M, et al. Autosomal dominant sensory/motor neuropathy with Ataxia (SMNA): Linkage to chromosome 7q22-q32. Am J Med Genet. 2002 May 8. 114(4):450-7. [Medline].

  72. Schelhaas HJ, Ippel PF, Hageman G, et al. Clinical and genetic analysis of a four-generation family with a distinct autosomal dominant cerebellar ataxia. J Neurol. 2001 Feb. 248(2):113-20. [Medline].

  73. Verbeek DS, Schelhaas JH, Ippel EF, et al. Identification of a novel SCA locus (SCA19) in a Dutch autosomal dominant cerebellar ataxia family on chromosome region 1p21-q21. Hum Genet. 2002 Oct. 111(4-5):388-93. [Medline].

  74. Chung MY, Lu YC, Cheng NC, Soong BW. A novel autosomal dominant spinocerebellar ataxia (SCA22) linked to chromosome 1p21-q23. Brain. 2003. June; 126(Pt 6):1293-9. [Medline].

  75. Schelhaas HJ, Verbeek DS, Van de Warrenburg BP, Sinke RJ. SCA19 and SCA22: evidence for one locus with a worldwide distribution. Brain. 2004 Jan. 127(Pt 1):E6; author reply E7. [Medline].

  76. Knight MA, Gardner RJ, Bahlo M, et al. Dominantly inherited ataxia and dysphonia with dentate calcification: spinocerebellar ataxia type 20. Brain. 2004 May. 127(Pt 5):1172-81. [Medline].

  77. Devos D, Schraen-Maschke S, Vuillaume I, et al. Clinical features and genetic analysis of a new form of spinocerebellar ataxia. Neurology. 2001 Jan 23. 56(2):234-8. [Medline].

  78. Vuillaume I, Devos D, Schraen-Maschke S, et al. A new locus for spinocerebellar ataxia (SCA21) maps to chromosome 7p21.3-p15.1. Ann Neurol. 2002 Nov. 52(5):666-70. [Medline].

  79. Verbeek DS, van de Warrenburg BP, Wesseling P, et al. Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13-12.3. Brain. 2004 Nov. 127(Pt 11):2551-7. [Medline].

  80. Stevanin G, Bouslam N, Thobois S, et al. Spinocerebellar ataxia with sensory neuropathy (SCA25) maps to chromosome 2p. Ann Neurol. 2004 Jan. 55(1):97-104. [Medline].

  81. Yu GY, Howell MJ, Roller MJ, et al. Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6. Ann Neurol. 2005 Mar. 57(3):349-54. [Medline].

  82. van Swieten JC, Brusse E, de Graaf BM, et al. A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia [corrected]. Am J Hum Genet. 2003 Jan. 72(1):191-9. [Medline].

  83. Cagnoli C, Mariotti C, Taroni F, et al. SCA28, a novel form of autosomal dominant cerebellar ataxia on chromosome 18p11.22-q11.2. Brain. 2006 Jan. 129(Pt 1):235-42. [Medline].

  84. Naito H, Oyanagi S. Familial myoclonus epilepsy and choreoathetosis: hereditary dentatorubral-pallidoluysian atrophy. Neurology. 1982 Aug. 32(8):798-807. [Medline].

  85. Koide R, Ikeuchi T, Onodera O, et al. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nat Genet. 1994 Jan. 6(1):9-13. [Medline].

  86. VanDyke DH, Griggs RC, Murphy MJ, Goldstein MN. Hereditary myokymia and periodic ataxia. J Neurol Sci. 1975 May. 25(1):109-18. [Medline].

  87. Hanson PA, Martinez LB, Cassidy R. Contractures, continuous muscle discharges, and titubation. Ann Neurol. 1977 Feb. 1(2):120-4. [Medline].

  88. Gancher ST, Nutt JG. Autosomal dominant episodic ataxia: a heterogeneous syndrome. Mov Disord. 1986. 1(4):239-53. [Medline].

  89. Browne DL, Gancher ST, Nutt JG, et al. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nat Genet. 1994 Oct. 8(2):136-40. [Medline].

  90. Brandt T, Strupp M. Episodic ataxia type 1 and 2 (familial periodic ataxia/vertigo). Audiol Neurootol. 1997 Nov-Dec. 2(6):373-83. [Medline].

  91. Eunson LH, Rea R, Zuberi SM, et al. Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability. Ann Neurol. 2000 Oct. 48(4):647-56. [Medline].

  92. Parker HL. Periodic ataxia. Collected Papers of the Mayo Clinic. 1946. 642-5.

  93. White JC. Familial periodic nystagmus, vertigo, and ataxia. Arch Neurol. 1969 Mar. 20(3):276-80. [Medline].

  94. Subramony SH, Schott K, Raike RS, et al. Novel CACNA1A mutation causes febrile episodic ataxia with interictal cerebellar deficits. Ann Neurol. 2003 Dec. 54(6):725-31. [Medline].

  95. Spacey SD, Materek LA, Szczygielski BI, Bird TD. Two novel CACNA1A gene mutations associated with episodic ataxia type 2 and interictal dystonia. Arch Neurol. 2005 Feb. 62(2):314-6. [Medline].

  96. Imbrici P, Eunson LH, Graves TD, et al. Late-onset episodic ataxia type 2 due to an in-frame insertion in CACNA1A. Neurology. 2005 Sep 27. 65(6):944-6. [Medline].

  97. Steckley JL, Ebers GC, Cader MZ, McLachlan RS. An autosomal dominant disorder with episodic ataxia, vertigo, and tinnitus. Neurology. 2001 Oct 23. 57(8):1499-502. [Medline].

  98. Cader MZ, Steckley JL, Dyment DA, et al. A genome-wide screen and linkage mapping for a large pedigree with episodic ataxia. Neurology. 2005 Jul 12. 65(1):156-8. [Medline].

  99. Farmer TW, Mustain VM. Vestibulocerebellar ataxia. A newly defined hereditary syndrome with periodic manifestations. Arch Neurol. 1963 May. 8:471-80. [Medline].

  100. Vance JM, Pericak-Vance MA, Payne CS. Linkage and genetic analysis in adult onset periodic vestibulo-cerebellar ataxia: report of a new family. Am J Hum Genet. 1984. 36:78S.

  101. Damji KF, Allingham RR, Pollock SC, et al. Periodic vestibulocerebellar ataxia, an autosomal dominant ataxia with defective smooth pursuit, is genetically distinct from other autosomal dominant ataxias. Arch Neurol. 1996 Apr. 53(4):338-44. [Medline].

  102. Escayg A, Jones JM, Kearney JA, et al. Calcium channel beta 4 (CACNB4): human ortholog of the mouse epilepsy gene lethargic. Genomics. 1998 May 15. 50(1):14-22. [Medline].

  103. Escayg A, De Waard M, Lee DD, et al. Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet. 2000 May. 66(5):1531-9. [Medline].

  104. Herrmann A, Braathen GJ, Russell MB. [Episodic ataxias]. Tidsskr Nor Laegeforen. 2005 Aug 11. 125(15):2005-7. [Medline].

  105. Auburger G, Ratzlaff T, Lunkes A, et al. A gene for autosomal dominant paroxysmal choreoathetosis/spasticity (CSE) maps to the vicinity of a potassium channel gene cluster on chromosome 1p, probably within 2 cM between D1S443 and D1S197. Genomics. 1996 Jan 1. 31(1):90-4. [Medline].

  106. Müller U, Steinberger D, Németh AH. Clinical and molecular genetics of primary dystonias. Neurogenetics. 1998 Mar. 1(3):165-77. [Medline].

  107. Ferguson FR, Critchley M. A clinical study of an heredo-familial disease resembling disseminated sclerosis. Brain. 1929. 52:203-25.

  108. Gayle Jr RF, Williams JP. A familial disease of the central nervous system resembling multiple sclerosis. Sth Med J. 1933. 26:242-6.

  109. Mahloudji M. Hereditary spastic ataxia simulating disseminated sclerosis. J Neurol Neurosurg Psychiatry. 1963 Dec. 26:511-3. [Medline].

  110. Meijer IA, Hand CK, Grewal KK, et al. A locus for autosomal dominant hereditary spastic ataxia, SAX1, maps to chromosome 12p13. Am J Hum Genet. 2002 Mar. 70(3):763-9. [Medline].

  111. Grewal KK, Stefanelli MG, Meijer IA, et al. A founder effect in three large Newfoundland families with a novel clinically variable spastic ataxia and supranuclear gaze palsy. Am J Med Genet A. 2004. Dec 15;131(3):249-54. [Medline].

  112. Ochrynik T, Bulski T, Modzelewski M, Szatkowski M. Olivopontocerebellar atrophy in MRI spectroscopy- case report. Pol J Radiol. 2007. 72(pt 1):100-2.

  113. Takei A, Hamada T, Yabe I, Sasaki H. Treatment of cerebellar ataxia with 5-HT1A agonist. Cerebellum. 2005. 4(3):211-5. [Medline].

  114. Ogawa M. Pharmacological treatments of cerebellar ataxia. Cerebellum. 2004. 3(2):107-11. [Medline].

  115. Assadi M, Campellone JV, Janson CG, Veloski JJ, Schwartzman RJ, Leone P. Treatment of spinocerebellar ataxia with buspirone. J Neurol Sci. 2007 Sep 15. 260(1-2):143-6. [Medline].

  116. Dluzen DE, McDermott JL, Liu B. Estrogen as a neuroprotectant against MPTP-induced neurotoxicity in C57/B1 mice. Neurotoxicol Teratol. 1996 Sep-Oct. 18(5):603-6. [Medline].

  117. Al Sweidi S, Sánchez MG, Bourque M, Morissette M, Dluzen D, Di Paolo T. Oestrogen receptors and signalling pathways: implications for neuroprotective effects of sex steroids in Parkinson's disease. J Neuroendocrinol. 2012 Jan. 24(1):48-61. [Medline].

  118. D'Astous M, Morissette M, Di Paolo T. Effect of estrogen receptor agonists treatment in MPTP mice: evidence of neuroprotection by an ER alpha agonist. Neuropharmacology. 2004 Dec. 47(8):1180-8. [Medline].

  119. Gardiner SA, Morrison MF, Mozley PD, Mozley LH, Brensinger C, Bilker W, et al. Pilot study on the effect of estrogen replacement therapy on brain dopamine transporter availability in healthy, postmenopausal women. Am J Geriatr Psychiatry. 2004 Nov-Dec. 12(6):621-30. [Medline].

  120. Heo JH, Lee ST, Chu K, Kim M. The efficacy of combined estrogen and buspirone treatment in olivopontocerebellar atrophy. J Neurol Sci. 2008 Aug 15. 271(1-2):87-90. [Medline].

  121. Ristori G, Romano S, Visconti A, Cannoni S, Spadaro M, Frontali M, et al. Riluzole in cerebellar ataxia: a randomized, double-blind, placebo-controlled pilot trial. Neurology. 2010 Mar 9. 74(10):839-45. [Medline].

  122. Landers M, Adams M, Acosta K, Fox A. Challenge-oriented gait and balance training in sporadic olivopontocerebellar atrophy: a case study. J Neurol Phys Ther. 2009 Sep. 33(3):160-8. [Medline].

  123. Armstrong RA, Lantos PL, Cairns NJ. Spatial patterns of alpha-synuclein positive glial cytoplasmic inclusions in multiple system atrophy. Mov Disord. 2004 Jan. 19(1):109-12. [Medline].

  124. Barth PG, Blennow G, Lenard HG, et al. The syndrome of autosomal recessive pontocerebellar hypoplasia, microcephaly, and extrapyramidal dyskinesia (pontocerebellar hypoplasia type 2): compiled data from 10 pedigrees. Neurology. 1995 Feb. 45(2):311-7. [Medline].

  125. Barth PG, Vrensen GF, Uylings HB, et al. Inherited syndrome of microcephaly, dyskinesia and pontocerebellar hypoplasia: a systemic atrophy with early onset. J Neurol Sci. 1990 Jun. 97(1):25-42. [Medline].

  126. Berciano J. Olivopontocerebellar atrophy. A review of 117 cases. J Neurol Sci. 1982 Feb. 53(2):253-72. [Medline].

  127. Berciano J, Boesch S, Pérez-Ramos JM, Wenning GK. Olivopontocerebellar atrophy: toward a better nosological definition. Mov Disord. 2006 Oct. 21(10):1607-13. [Medline].

  128. Berciano J, Tolosa E. Olivopontocerebellar atrophy. Jankovic J, Tolosa E, eds. Parkinson's Disease and Movement Disorders. Baltimore, Md: Williams & Wilkins; 1993. 163-89.

  129. Berent S, Giordani B, Gilman S, et al. Patterns of neuropsychological performance in multiple system atrophy compared to sporadic and hereditary olivopontocerebellar atrophy. Brain Cogn. 2002 Nov. 50(2):194-206. [Medline].

  130. Bird TD. Hereditary Ataxia Overview. GeneReviews. 2006. [Full Text].

  131. Boder E, Sedgwick RP. Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. Pediatrics. 1958. Apr; 21(4):526-54. [Medline].

  132. Brown S. On hereditary ataxia, with a series of twenty-one cases. Brain. 1892. 15:250-82.

  133. Cervinkova M, Mandakova P, Síma P. Changes in proliferation activity and relative distributions of lymphoid cell subpopulations in congenitally athymic nu/nu mice and Lurcher mice with spontaneous olivopontocerebellar degeneration. Folia Microbiol (Praha). 2006. 51(5):497-505. [Medline].

  134. Chokroverty S, Khedekar R, Derby B, et al. Pathology of olivopontocerebellar atrophy with glutamate dehydrogenase deficiency. Neurology. 1984 Nov. 34(11):1451-5. [Medline].

  135. Dekoskey ST, Kaufer DI, Lopez OL. Bradley WG, Daroff, RB, Fenichel GM, Jankovic J, eds. Neurology in Clinical Practice. Boston, Mass: Butterworth-Heinemann; 2005. 1928.

  136. Duvoisin RC, Chokroverty S, Lepore F, Nicklas W. Glutamate dehydrogenase deficiency in patients with olivopontocerebellar atrophy. Neurology. 1983 Oct. 33(10):1322-6. [Medline].

  137. Fahn S, Przedborski S. Parkinsonism: multiple system atrophy. Rowland L, ed. Merritt's Neurology. 11th ed. New York, NY: Lippincott Williams & Wilkins; 2005. 836-7.

  138. Hammond EJ, Wilder BJ. Evoked potentials in olivopontocerebellar atrophy. Arch Neurol. 1983 Jun. 40(6):366-9. [Medline].

  139. Holmes GM. A form of familial degeneration of the cerebellum. Brain. 1907. 30:466-89.

  140. Ishizawa K, Komori T, Arai N, Mizutani T, Hirose T. Glial cytoplasmic inclusions and tissue injury in multiple system atrophy: A quantitative study in white matter (olivopontocerebellar system) and gray matter (nigrostriatal system). Neuropathology. 2008 Jun. 28(3):249-57. [Medline].

  141. Koeppen AH. The hereditary ataxias. J Neuropathol Exp Neurol. 1998 Jun. 57(6):531-43. [Medline].

  142. Kofler M, Muller J, Seppi K, Wenning GK. Exaggerated auditory startle responses in multiple system atrophy: a comparative study of parkinson and cerebellar subtypes. Clin Neurophysiol. 2003 Mar. 114(3):541-7. [Medline].

  143. Kuriyama N, Mizuno T, Iida A, et al. Autonomic nervous evaluation in the early stages of olivopontocerebellar atrophy. Auton Neurosci. 2005 Dec 30. 123(1-2):87-93. [Medline].

  144. Landis DM, Rosenberg RN, Landis SC, et al. Olivopontocerebellar degeneration. Clinical and ultrastructural abnormalities. Arch Neurol. 1974 Nov. 31(5):295-307. [Medline].

  145. Louis-Bar D. Sur un syndrome progressif cormprenant des telangiectasies capillaires cutanees et conjonctivales symetriques, e disposition naevoïde et des troubles cerebelleux. Confinia Neurologica. 1941. 4:32-42.

  146. Luo W, Ouyang Z, Guo Y, Chen Y, Ding M. Spinal muscular atrophy combined with sporadic olivopontocerebellar atrophy. Clin Neurol Neurosurg. 2008 Sep. 110(8):855-8. [Medline].

  147. Mascalchi M, Cosottini M, Lolli F, Salvi F, Tessa C, Macucci M, et al. Proton MR spectroscopy of the cerebellum and pons in patients with degenerative ataxia. Radiology. 2002 May. 223(2):371-8. [Medline].

  148. McKusick VA et al. Online Mendelian Inheritance in Man (OMIM). [Full Text].

  149. Nonne M. Uber eine eigentumliche familiare Erkrankungsform des Zentralnervensystems. Archiv Psychiatrie Nervenkrankheiten, Berlin. 1891. 22:283-316.

  150. Oshima K. Olivopontocerebellar atrophy (OPCA) in corticobasal degeneration (CBD): a quantitative study of three cases of atypical CBD: OI-A22. Neuropathology. 2007. 27(pt 2):166.

  151. Papp MI, Kahn JE, Lantos PL. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci. 1989 Dec. 94(1-3):79-100. [Medline].

  152. Papp MI, Lantos PL. Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy. J Neurol Sci. 1992 Feb. 107(2):172-82. [Medline].

  153. Penney JB. Multiple systems atrophy and nonfamilial olivopontocerebellar atrophy are the same disease. Ann Neurol. 1995 May. 37(5):553-4. [Medline].

  154. Rinne JO, Burn DJ, Mathias CJ, et al. Positron emission tomography studies on the dopaminergic system and striatal opioid binding in the olivopontocerebellar atrophy variant of multiple system atrophy. Ann Neurol. 1995 May. 37(5):568-73. [Medline].

  155. Roper AH, Brown RH. Adam's and Victor's The Principles of Neurology. 8th ed. New York, NY: McGraw-Hill; 2005. 925-6; 935-6.

  156. Sorbi S, Tonini S, Giannini E, et al. Abnormal platelet glutamate dehydrogenase activity and activation in dominant and nondominant olivopontocerebellar atrophy. Ann Neurol. 1986 Mar. 19(3):239-45. [Medline].

  157. Syllaba L, Henner K. Contribution a l'etude de l'indendance de l'athetose double idiopathique et congenitale. Atteinte familiale, syndrome dystrophique, signe du resau vasculaire conjonctival, integrite psychique. Revue neurologique. 1926. 1:541-60.

  158. Testa D, Tiranti V, Girotti F. Unusual association of sporadic olivopontocerebellar atrophy and motor neuron disease. Neurol Sci. 2002 Dec. 23(5):243-5. [Medline].

  159. Jellinger KA. Neuropathology of multiple system atrophy: New thoughts about pathogenesis. Mov Disord. 2014 Oct 9. [Medline].

  160. Meissner WG, Flabeau O, Perez P, Taillard J, Marquant F, Dupouy S, et al. Accuracy of portable polygraphy for the diagnosis of sleep apnea in multiple system atrophy. Sleep Med. 2014 Apr. 15(4):476-9. [Medline].

  161. Kuzdas-Wood D, Stefanova N, Jellinger KA, Seppi K, Schlossmacher MG, Poewe W, et al. Towards translational therapies for multiple system atrophy. Prog Neurobiol. 2014 Jul. 118:19-35. [Medline]. [Full Text].

Table 1. Most Common OPCAs With Alternative Names
OMIM #OPCA NamesOther NamesGenetic PatternDescription


Menzel type OPCA





Gene map locus 6p23 expanded (CAG)n trinucleotide repeat in the ataxin-1 gene (ATXN1; 601556); autosomal dominant; genetic test availableOnset 30-40 years; ataxia, spasticity, dysarthria, ophthalmoplegia, slow saccades, nystagmus, optic atrophy, pyramidal tract signs; rare extrapyramidal signs; some have dementia; neuropathy occurs late[15]
#183090OPCA-2SCA-2, ADCA-IGene map locus 12q24 expanded (CAG)n trinucleotide repeat in the gene encoding ataxin-2 (ATXN2; 601517); autosomal dominant; genetic test availableOnset in 30s; ataxia, dysarthria, muscle cramps; slow saccades; ophthalmoplegia; peripheral neuropathy; dementia (some); no pyramidal or extrapyramidal features[16]
%258300OPCA-II, Fickler-Winkler type OPCAFickler-Winkler SyndromeGene/biochemistry not known; autosomal recessiveAdult-onset; cerebellar ataxia, albinism, impaired intellect; neurological impairments similar to OPCA-I but no involuntary movements or sensory loss[9, 17, 18]
#164500OPCA-III, OPCA-3, OPCA with retinal degenerationADCA-II, SCA-7, OPCA with macular degeneration and external ophthalmoplegiaGene locus 3p21.1-p12; expanded trinucleotide repeat in the gene encoding ataxin-7 (ATXN7; 607640); autosomal dominant; genetic test availableOnset in mid 20s; initially pigmentary retinal degeneration then ataxia, dysarthria, ophthalmoplegia, slow saccades, pyramidal tract signs[16]
^ 164600 Number now obsolete; considered the same as # 164400 (see first row above)OPCA-IV, Schut-Haymaker type OPCA Genetics unclear; glutamate dehydrogenase deficiency suspected in some; some cases may be linked to OPCA locus at chromosome 6p; may not be a pure genetic type; now thought to be same as OPCA-I (SCA-1) Adult-onset ataxia with involvement of cranial nerves IX, X, and XII[19]
164700OPCA-V, OPCA-5, OPCA with dementia and extrapyramidal signsThis may be the same as SCA-17Autosomal dominant; genetic test available for SCA-17, but unclear if this is the sameCerebellar ataxia, rigidity, dementia; neuronal loss in cerebellum, basal ganglia, substantia nigra, olivary nuclei, cerebral cortex[20, 8]
%302500OPCA-X, OPCA X-linked-1SCA-X1 (do not confuse this with SAX-1, the locus for hereditary (autosomal dominant) spastic ataxia [%108600])X-linked, some cases linked to Xp11.21-q21.3; not homogenous; gene(s) not knownOnset in first or second decade and often bedbound by 20s; loss of cerebellar Purkinje cells, inferior olivary cells, myelin loss in spinocerebellar tracts, posterior columns, and corticospinal tracts; gait and limb ataxia, intention tremor, dysmetria, dysdiadochokinesia, dysarthria, and nystagmus; some have peripheral neuropathy[21, 22]
Table 2. Extremely Rare Types of OPCAs
OMIM #OPCA NamesOther NamesGenetic PatternDescription
%607596Pontocerebellar hypoplasia type 1, PCH-1Pontocerebellar hypoplasia with infantile spinal muscular atrophy, pontocerebellar hypoplasia with anterior horn cell diseaseAutosomal recessiveCerebellar hypoplasia plus motor neuron loss; sometimes called a combination of olivopontocerebellar degeneration plus spinal muscular atrophy; present from birth; patients usually die in infancy[23, 24]
%277470Pontocerebellar hypoplasia type 2, PCH-2Pontocerebellar hypoplasia with progressive cerebral atrophy, Volendam neurodegenerative diseaseAutosomal recessiveCongenital microcephaly, extrapyramidal findings, epilepsy; autopsy in one case showed that the olivopontocerebellar system was the most heavily involved in degeneration
%608027Pontocerebellar hypoplasia type, PCH-3, Pontocerebellar hypoplasia with optic atrophyCerebellar atrophy with progressive microcephaly, CLAMAutosomal recessive; gene map locus 7q11-q21Gene map locus 7q11-q21Onset in infancy or childhood, cerebellar atrophy with progressive microcephaly; on MRI of small brainstem, small cerebellar vermis and atrophy of the cerebellum and cerebrum; ataxia, truncal hypotonia, and exaggerated deep tendon reflexes; one patient had optic atrophy; seizures common[25]
225753Pontocerebellar hypoplasia type 4, PCH-4Fatal infantile encephalopathy with olivopontocerebellar hypoplasiaProbably autosomal recessive, possibly autosomal dominant or maternal transmission; biochemical defect and gene locus not known Patients die in infancy; severe olivopontocerebellar hypoplasia on autopsy[26, 27]
610204Pontocerebellar hypoplasia type 5, PCH-5Olivopontocerebellar hypoplasia, fetal onsetGenetics not clearPontocerebellar hypoplasia is a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem with significant hypoplasia of the olivae, the pons, and the cerebellum; patients typically die in infancy[27]
#278800De Sanctis-Cacchione syndrome Gene map locus 10q11; an excision repair gene named variously ERCC6, CKN2, COFS, and CSB causing Cockayne syndrome type B (CSB; 133540) or genes of xeroderma pigmentosum, usually XPA (ie, complementation group A); 278700 9q22.3 or more rarely, other genes associated with xeroderma pigmentosum; autosomal recessive Xeroderma pigmentosum (severe sun sensitivity), mental retardation, dwarfism, and progressive neurological deterioration; overlaps with known types of xeroderma pigmentosum and Cockayne syndrome, especially XPA and CSB, apparently as allelic variants but other unknown factors may bring out the olivopontocerebellar (and cerebral) atrophy[28, 29, 30]
#212065Congenital disorder of glycosylation, type Ia Phosphomannomutase-2 (PMM2; 601785); autosomal recessiveSevere congenital psychomotor retardation, generalized hypotonia, hyporeflexia, and trunk ataxia, neonatal-onset OPCA, peripheral neuropathy, retinitis pigmentosa; defects in other systems include heart and musculoskeletal systems; severe neonatal neurodegenerative disease; some patients have olivopontocerebellar phenotype; usually death in infancy or childhood[31, 32]
Table 3. Dominant SCAs with OPCAs Identified
Disease OMIM #Disease NamesLocusGeneProduct (OMIM #)DescriptionReferences
#164400SCA-1, OPCA-I, OPCA-IV (OPCA-IV same as OPCA-I), ADCA-1ATXN1, 6p23CAG expansion repeat in N-terminal coding region of Ataxin-1 (*601556);Onset 30-40 years; ataxia, spasticity, dysarthria, ophthalmoplegia, slow saccades, nystagmus, optic atrophy, pyramidal tract signs; rare extrapyramidal; signs; some have dementia; neuropathy occurs late. Expansion repeat causes toxic gain of function via abnormally long ataxin-1. This worsens in subsequent generations. Menzel, 1891[33] ; Waggoner et al, 1938[34] ; Schut, 1950[35] ; Schut and Haymaker, 1951[19] ; Orr et al, 1993[36]

Donato et al. 2012[37]

#183090SCA-2, OPCA-2, ADCA-1ATXN2, 12q24Ataxin-2 (601517); genetic test availableOnset in 30s; ataxia, dysarthria, muscle cramps; slow saccades/ophthalmoplegia; peripheral neuropathy, hyporeflexia, dementia in some; no pyramidal or extrapyramidal features Boller and Segarra, 1969[38] ; Wadia and Swami, 1971[39] ; Ueyama et al, 1998[40]
#109150SCA-3 or Machado-Joseph disease, ADCA-1ATXN3, 14q24.3-q31Machado-Joseph disease protein 1(ATXN3). (607047); genetic test availableAll have ataxia, dysarthria, ophthalmoplegia; type I onset in mid 20s with facial-lingual myokymia, pyramidal and extrapyramidal features; type II onset in 40s; type III onset in mid 40s with peripheral neuropathy (weakness and atrophy) Nakano et al, 1972[41] ; Kawaguchi et al, 1994[42]
%600223SCA-4, ADCA-1Gene unknown, 16q22.1 (same region as #117210 below) Onset average approximately 40 years (range, 19-72 y); pure ataxia in some cases, most have sensory axonal neuropathy; deafness in some Gardner et al, 1994[43] ; Hellenbroich et al, 2003[44]
#117210SCA, 16q22-linked ADCA-3PLEKHG4, 16q22.1Puratrophin-1 (609526)Typically pure cerebellar ataxia with gait ataxia, cerebellar dysarthria, limb ataxia, decreased muscle tone, horizontal-gaze nystagmus; lacks other feature seen in SCA-4, ADCA-1 (but sometimes called SCA-4) Ishikawa et al, 2005[45]
#600224SCA-5, ADCA-3SPTBN2, 11p13Spectrin beta chain, brain 2 (604985)Onset mid 30s; downbeat nystagmus; ataxia, dysarthria, impaired smooth pursuit, and gaze-evoked nystagmus; slow progression; both vermal and hemispheric cerebellar atrophy, normal life expectancy Ikeda et al, 2006[46]
#183086SCA-6, ADCA-1 ADCA-3CACNA1A, 19p13Voltage-dependent P/Q-type Ca+2 channel alpha-1a subunit (601011); genetic test availableOnset 20-40 years; ataxia, dysarthria, nystagmus, distal sensory loss, normal life expectancySubramony et al, 1996[47] ; Zhuchenko et al, 1997[48]
#164500SCA-7, OPCA-3 ADCA-2ATXN7, 3p21.1-p12Ataxin-7 (607640); genetic test availableOnset mid 20s; pigmentary retinal degeneration, ataxia, dysarthria, ophthalmoplegia, slow saccades, pyramidal tract signsDavid et al, 1997[49] ; Harding, 1982[7]
#608768SCA-8, ADCA-2KLHL1AS, 13q21Genetic test availableOnset 20s to 70s; ataxia, dysarthria, nystagmus, impaired smooth pursuitKoob et al, 1999[50] ; Ikeda et al, 2000[51] ; Factor et al, 2005[52] (Factor et al case was actually consistent with MSA)
 SCA-9Unassigned category Unassigned categoryUnassigned category
+603516SCA-10 ADCA-3ATXN10, 22q13Ataxin-10; genetic test availableOnset in 20s; ataxia, dysarthria, nystagmus, epileptic seizures; to date only found in Mexican familiesGrewal et al, 1998[53] ; Zu et al, 1999[54] ; Grewal et al, 2002[55]
%604432SCA-11SCA11, 15q14-q21.3Tau-tubulin kinase 2Onset at 20-40 years; ataxia, dysarthria, nystagmusWorth et al, 1999[56]
#604326SCA-12PPP2R2B, 5q31-q33Serine/threonine protein phosphatase 2A, 55-kd regulatory subunit B, beta isoform; genetic test availableOnset at 8-55 years, commonly 30s; upper extremity and head tremor, gait ataxia, ophthalmoplegia, hyperreflexia, bradykinesia, dementia Holmes et al, 1999[57] ; Fujigasaki et al, 2001[58]
#605259SCA-13KCNC3, 19q13.3-q13.4Voltage-gated K+ channel, subfamily C member 3Onset in childhood; ataxia, dysarthria, mental retardation; slow progressionWaters et al, 2006[59]
#605361SCA-14PRKCG, 19q13.4Kinase C, gamma type; genetic test availableOnset mostly in most those older than 39 years; ataxia, dysarthria, nystagmus; younger patients (< 27 y) also had intermittent axial myoclonus prior to ataxia Yamashita et al 2000[60] ; Brkanac, Bylenok et al 2002[61] ; Chen, Brkanac et al 2003[62] ; Yabe et al 2003[63]
%606658SCA-15Gene unknown, 3p26.1-p25.3Inositol 1,4,5-triphosphate receptor type 1Similar to SCA-6 and SCA-8; MRI-proven cerebellar atrophy; onset at 10-50 years; slowly progressive pure cerebellar ataxia, ataxic dysarthria, tremor; may have head titubation, nystagmus, oculovestibular reflex abnormalities, mild hyperreflexia (no spasticity or Babinski signs) Storey et al, 2001[64] ; Knight et al, 2003[65] ; Hara et al, 2004[66]
%606364SCA-16SCA16, 8q22.1-q24.1Contactin-4MRI-proven cerebellar atrophy without brainstem involvement; onset at 20-66 years; pure cerebellar ataxia, some with head tremor, slow progression Miyoshi et al, 2001[67]
#607136SCA-17, may be OPCA-5TBP, 6q27TATA-box–binding protein; genetic test availableOnset at 3-55 years; ataxia and involvement of pyramidal, extrapyramidal, and, possibly autonomic system; intellectual impairment, dementia, psychosis, chorea; presentation similar to Huntington disease; degeneration of caudate, putamen, thalamus, frontal cortex, temporal cortex, and cerebellum Nakamura et al, 2001[68] ; Rolfs et al, 2003[69] ; Maltecca et al, 2003[70]
%607458SCA-18SCA18 7q22-q32 Onset in teens, 20s, and 30s; sensorimotor neuropathy with ataxia; gait abnormality, dysmetria, hyporeflexia, muscle weakness and atrophy, axonal neuropathy, decreased vibratory and proprioceptive sense Brkanac et al, 2002[71]
%607346SCA-191p21-q21 Onset at 12-40 years; gait and limb ataxia, hyporeflexia, dysphagia, dysarthria, and gaze-evoked horizontal nystagmus; cerebellar atrophy on MRIs Schelhaas et al, 2001[72] ; Verbeek et al, 2002[73] ; Chung et al, 2003[74] ; Schelhaas et al, 2004[75]
%608687SCA-20SCA20, 11p13-q11 Onset at 19-64 years; dysarthria, gait ataxia, upper limb, slow progression; more variable features are mild pyramidal signs, hypermetric saccades, nystagmus, palatal tremor, slow cognitive decline; CT scan shows dentate calcification Knight et al, 2004[76]
%607454SCA-21SCA21, 7p21-15 Onset at 6-30 years; cerebellar ataxia, limb ataxia and akinesia, dysarthria, dysgraphia, hyporeflexia, postural tremor, resting tremor, rigidity, cognitive impairment, cerebellar atrophy Devos et al, 2001[77] ; Vuillaume et al, 2002[78]
%607346SCA-221p21-q21 Now believed to be identical to SCA-19 (Schelhaas et al, 2004[75] ) though Chung et al (2004)[74] dispute this Schelhaas et al, 2001[72] ; Verbeek et al, 2002[73] ; Chung et al, 2004[74] ; Schelhaas et al, 2004[75]
%610245SCA-2320p13-12.3 Onset at 40s and 50s; slow progression; gait and limb ataxia, dysarthria (varies), slow saccades and ocular dysmetria, decreased vibratory sense; severe cerebellar atrophy Verbeek, et al, 2004[79]
%608703SCA-25SCA25, 2p21-p13 Onset in childhood; invariable features are cerebellar ataxia; variable features are lower limb areflexia, peripheral sensory neuropathy, nystagmus, decreased visual acuity, facial tics, extensor plantar responses, urinary urgency, and gastrointestinal symptoms Stevanin et al, 2004[80]
%609306SCA-2619p13.3 Onset t 25-60 years; pure cerebellar signs, including ataxia of the trunk and limbs, dysarthria, and irregular visual pursuit movements; intelligence normal; MRI shows atrophy of cerebellum, sparing pons and medulla Yu et al, 2005[81]
#609307SCA-27FGF14, 13q34Fibroblast growth factor 14 (601515)Onset in childhood; cerebellar ataxia, tremor, low IQ, aggressive behavior, eye movement abnormalities are nystagmus, cerebellar dysarthria, head tremor, orofacial dyskinesias, cerebellar atrophy, pes cavus, axonal sensory neuropathy, neuronal loss in cerebral cortex, amygdala, and basal ganglia van Swieten et al, 2003[82]
%610246SCA-2818p11.22-q11.2AFG3-like protein 2Onset at 19.5 years (range, 12-36 y); imbalance and mild gait incoordination; gaze-evoked nystagmus, slow saccades, ophthalmoparesis, and, often, ptosis; frequently lower limb hyporeflexia Cagnoli et al, 2006[83]
#125370Dentatorubral-pallidoluysian atrophy (DRPLA)DRPLA, 12p13.31Atropin-1–related protein (607462); genetic test availableOnset in 20s to 30s; myoclonic epilepsy, dementia, ataxia, choreoathetosis, degeneration of dentatorubral and pallidoluysian systems Naito and Oyanagi, 1982[84] ; Koide et al, 1994[85]
#160120Episodic ataxia type 1, EA-1KCNA1, 12p13K+1 voltage-gated channel (A1) (600111); genetic test available on research basisOnset usually in childhood; continuous muscle movement (myokymia) and periodic ataxiaVan Dyke et al, 1975[86] ; Hanson et al, 1977[87] ; Gancher and Nutt, 1986[88] ; Browne et al, 1994[89] ; Brandt and Strupp, 1997[90] ; Eunson et al, 2000[91]
#108500Episodic ataxia type 2, EA-2CACNA 1A, 19p13Voltage-dependent P/Q-type Ca+2 channel alpha-1A subunit (601011); genetic test available on research basisOnset in childhood; ataxia, downbeating nystagmus dizziness treated with acetazolamide; no progression after childhood; cerebellar atrophy Parker, 1946[92] ; White, 1969[93] ; Subramony et al, 2003[94] ; Spacey et al, 2005[95] ; Imbrici et al, 2005[96]
%606554Episodic ataxia type 3, EA-31q42UnknownOnset at 1-42 years; vestibular ataxia, vertigo, tinnitus, interictal myokymiaSteckley et al, 2001[97] ; Cader et al, 2005[98]
%606552Episodic ataxia type 4, EA-4UnknownUnknownOnset in third to sixth decade; recurrent attacks of vertigo, diplopia, and ataxia; slowly progressive cerebellar ataxia in some; periodic vestibulocerebellar ataxia in an autosomal dominant pedigree pattern, defective smooth pursuit, gaze-evoked nystagmus, ataxia, vertigo Farmer and Mustian, 1963[99] ; Vance et al, 1984[100] ; Damji et al, 1996[101]
+601949Episodic ataxia type 5, EA-5CACNB 4, 2q22-q23Voltage-dependent L-type calcium beta-4 subunit (+601949)Onset in third or fourth decade; mutation at C104F in French-Canadian family; ataxia similar to EA-2; severe episodic lasting hours to weeks; treatment with acetazolamide; interictal ataxia includes gait and truncal, mild dysarthria; nystagmus (downbeat, spontaneous, gaze evoked); seizures Escayg et al, 1998[102] ; Escayg et al, 2000[103] ; Herrmann et al, 2005[104]
%601042Choreoathetosis spasticity, episodic, CSE12p13 (close to potassium channel gene KCNA1 but not the same)UnknownOnset at 2-15 years; paroxysmal choreoathetosis with episodic ataxia and spasticityAuburger et al, 1996[105] ; Müller et al, 1998[106]
%108600Hereditary (autosomal dominant) spastic ataxiaSAX1, 12p13UnknownOnset at 10-20 years; lower limb spasticity, generalized ataxia with dysarthria, dysphagia, impaired ocular movements, gait abnormalities; brain and cord MRIs normal; neuropathology shows midbrain neuronal loss Ferguson and Critchley, 1929[107] ; Gayle and Williams, 1933[108] ; Mahloudji, 1963[109] ; Meijer et al, 2002[110] ; Grewal et al, 2004[111]
Table 4. Dominant Ataxia Nomenclature
SCAsSCA-1SCA-2SCA-3SCA types 8, 12, 17, 25, 27, 28, (13)SCA-7SCAs 4, 5, 6, 10, 11, 14, 15, 22, 26, (13)
OPCAsOPCA-1, OPCA-IVOPCA-2No OPCA matching SCA-3No OPCA matching above SCAsOPCA-IIINo OPCA matching above SCAs
EponymsMenzel type OPCA (or Menzel ataxia), Schut- Haymaker type OPCA, Dejerine-Thomas ataxiaHolguin type ataxia, Wadia-Swami syndrome, Dejerine-Thomas ataxiaMachado-Joseph disease, Dejerine-Thomas ataxiaDejerine-Thomas ataxiaSanger-Brown ataxia§, Dejerine-Thomas ataxiaHolmes ataxiall, ataxia of Marie, Foix, and Alajouanine, Marie ataxia, Nonne syndrome#
*SCA-13 is often said to not be part of ADCA classification. It is mainly a childhood mental retardation/ataxia syndrome. The ataxia is not accompanied by significant brainstem pathology, similar to ADCA-3. The mental retardation can be interpreted as a dementia, putting it in ADCA-1.

OPCA-IV (Schut-Haymaker OPCA) is now thought to be an SCA-1, which makes it OPCA-I (ie, strictly speaking, OPCA-IV no longer exists).

Menzel OPCA is sometimes taken much more broadly as virtually any OPCA except perhaps OPCA-III. Alternatively, it is taken as essentially the same as ADCA-1. In addition, it is sometimes applied to sporadic OPCAs that have similar presentations to any of the syndromes under ADCA-1.

§ Sanger-Brown ataxia is sometimes taken more broadly. As expansively defined, the term could be used for virtually any of these.

ll Holmes ataxia is sometimes applied to pure sporadic cerebellar ataxia of late onset.

This is sometimes used for most any of these syndromes, which seems to be the sense in which it was used in the original 1893 paper by Marie.

# This is a very obscure term. It is most commonly used for conditions fitting ADCA-3.

**The authors found no papers calling SCA-3 Dejerine-Thomas ataxia, but Dejerine-Thomas ataxia is so broadly defined, the term could possibly be applied to SCA-3.

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.