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HEREDITARY ATAXIAS: DOMINANT

Spinocerebellar Ataxia (SCA)
1: Ataxin-1; CAG repeat; 6p22
2: Ataxin-2; CAG repeat; 12q24
3: Ataxin-3; CAG repeat; 14q32
4 (Sensory ataxia): 16q22
5: β-III Spectrin; 11q13
6: CACNA1A; CAG repeat; 19p13
7: Ataxin-7; CAG repeat; 3p21
8: ATXN8OS; CTG repeat; 13q21
9: ?
10: ATXN10; ATTCT repeat; 22q13
11: TTBK2; 15q14
12: PPP2R2B; CAG repeat; 5q31
13: KCNC3; 19q13.33
14: PRKCG; 19q13.42
15 & 16: ITPR1; 3p26
  29: 3p26
17: TBP; CAG repeat; 6q27
18: 7q31
19: KCND3; 1p13
20: 11q12, Duplication
21: TMEM240; 1p36
22: KCND3; 1p13
23: PDYN; 20p13
25: 2p15-p21
26: EEF2; 19p13
27: FGF14; 13q33
28: AFG3L2; 18p11
30: 4q34
31: TGGAA repeat; 16q22
32: 7q32
34: ELOVL4; 6q14
35: TGM6; 20p13
36: NOP56; 20p13
37: 1p32
38: ELOVL5; 6p12
40: CCDC88C; 14q32
Other dominant ataxia syndromes
Branchial myoclonus & Spasticity: GFAP; 17q21
CANPMR: CAMTA1; 1p36
CAPOS: ATP1A3; 19q13
Congenital ataxia
Cortical Myoclonus: NOL3; 16q22
Cough, Spasmodic
Deafness & Narcolepsy: DNMT1; 19p13
DRPLA: ATN1; CAG repeat; 12p13
Familial dementia: ITM2B; 13q14
Gillespie: PAX6; 11p13
Hemiplegia, alternating: 1; 2
Holmes ataxia
Huntington 2: JPH3; CAG/CTG repeat; 16q23
Leukodystrophy
  Adult-onset: Lamin B1; 5q23
  H-ABC: TUBB4A; 19p13
Multiple hamartoma syndrome: PTEN; 10q23
Myasthenia + CNS: SNAP25b; 20p12
Myelocerebellar
Neuronal intranuclear inclusion disease
Nystagmus
Parenchymal degeneration
Peripheral Neuropathy
  Rigidity
  Saccades slow + Orthostatism
  SANDO: POLG1; 15q25
  Sensory ataxia: 16q22
  Sensory-Motor: IFRD1; 7q22
  Thermoanalgesia & Fungiform papillae loss
Prion disease: Prion protein; 20p12
Seizures: SLC2A1; 1p35
SMEI: SCN1A; 2q24
SPAR
Spastic ataxia syndromes
Tremor, Essential: 3q13
Vanishing white matter
Vermal aplasia
Von Hippel-Lindau: VHL protein; 3p26
Episodic ataxias (EA): Usually Dominant
  EA 1 + Myokymia: KCNA 1; 12p13
  EA 2, Paroxysmal: α1A Ca++ channel; 19p13
  EA 3 + Vertigo & Tinnitus: 1q42
  EA 4 (PATX)
  EA5: CACNB4β4; 2q22
  EA6 + Migraine & CNS: SLC1A3; 5p13
  EA7: 19q13
  EA8: 1p36
  EA + Choreoathetosis & Spasticity: SLC2A1; 1p34
  PDHA1: Xp22; Recessive
  Differential diagnosis

SCA: Differential features

Ataxia Syndromes: Other
  Recessive
  X-linked
  Congenital
  DNA repair defects
  Metabolic disorders
  Mitochondrial
  Multisystem disorders
  Spastic
  Acquired


Cajal


Dominant Spinocerebellar Ataxia (SCA): General 35 Dominant Spinocerebellar Ataxia (SCA): Differential diagnosis 64

Age
Polyneuropathy
Syndromes
Other


Spinocerebellar Ataxia 1 (SCA 1) (ADCA I)
  Ataxin-1 (ATXN1) ; Chromosome 6p22.3; Dominant


SCA 2 (ADCA I) 1
  Ataxin-2 (ATXN2) ; Chromosome 12q24.12; Dominant


SCA 3 (Machado-Joseph) (ADCA I)
  Ataxin-3 (ATXN3; MJD gene) ; Chromosome 14q32.12; Dominant

SCA 4 (Sensory ataxic neuropathy 2)
  Chromosome 16q22.1; Dominant

SCA 5 (ADCA III) 33
  β-Spectrin, nonerythrocytic, 2 (β-III Spectrin; SPTBN2) ; Chromosome 11q13.2; Dominant

SCA 6 (ADCA III)
  Calcium channel, voltage dependent, P/Q type, α1A subunit (CACNA1A; CaV2.1) ; Chromosome 19p13.2; Dominant

SCA 7 (ADCA II)
  Ataxin-7 (ATXN7) ; Chromosome 3p14.1; Dominant

SCA 8 9: Involves CTA/CTG repeat expansion in 2 overlapping genes
  ATXN8OS (SCA8) ; Chromosome 13q21.33; Dominant (Usually)
  ATXN8 ; Chromosome 13q21; Dominant (Usually)

SCA 9 (ADCA I)
  Chromosome ?; Dominant

SCA 10 (ADCA III) 10
  Ataxin 10 (ATXN10; SCA 10 gene; E46L) ; Chromosome 22q13.31; Dominant

SCA 11 (ADCA III) 11
  tau tubulin kinase 2 (TTBK2) ; Chromosome 15q15.2; Dominant

SCA 12 12
  Protein phosphatase 2, regulatory subunit B, β (PPP2R2B) ; Chromosome 5q32; Dominant

SCA 13 13
  Potassium channel, voltage-gated, shaw-related subfamily, member 3 (KCNC3) ; Chromosome 19q13.33; Dominant

SCA 14 14
  Protein kinase Cγ (PRKCG) ; Chromosome 19q13.42; Dominant

SCA 15 16
  Inositol 1,4,5-triphosphate receptor, type 1 (ITPR1) ; Chromosome 3p26.1; Dominant

SCA 17: Ataxia with intellectual deterioration 18
  TATA box-binding protein (TBP) ; Chromosome 6q27; Dominant

SCA 18: Ataxia with sensory disorder and neurogenic muscular atrophy
  Chromosome 7q22-q32; Dominant



SCA 19: Ataxia with cognitive impairment 24
  KCND3 ; Chromosome 1p13.2; Dominant

SCA 22: Pure cerebellar ataxia 27
  KCND3 ; Chromosome 1p13.2; Dominant

SCA 20: Ataxia with Dysphonia & Dentate calcification 34
  Chromosome 11q12; Dominant

Ataxia with Spasmodic Cough 45
  Dominant

SCA 21: Ataxia with Cognitive impairment & Extrapyramidal 23
  Transmembrane protein 240 (TMEM240) ; Chromosome 1p36.33; Dominant

SCA 23 37
  Prodynorphin (PDYN) ; Chromosome 20p13; Dominant & Sporadic

SCA 25: Spinocerebellar ataxia & Sensory neuropathy 30
  Chromosome 2p21-p13; Dominant

SCA 26 : Pure cerebellar ataxia 41
  Eukaryotic translation elongation factor 2 (EEF2) Chromosome 19p13.3; Dominant

SCA 27: SCA with Tremor & Dyskinesia (ADCA I) 26
  Fibroblast growth factor 14 (FGF14) ; Chromosome 13q33.1; Dominant
SCA 28: SCA with Ophthalmoparesis & Hyperreflexia (ADCA I) 43
  ATPase family gene 3-like 2 (AFG3L2) ; Chromosome 18p11.21; Dominant

SCA 30: Pure cerebellar ataxia (ADCA III) 47
  Chromosome 4q34.3-q35.1; Dominant

SCA 31: Pure cerebellar ataxia (ADCA III) 52
  Brain-Expressed, Associated with NEDD4 (BEAN) ; Penta-nucleotide (TGGAA)n repeat insertion; Chromosome 16q21; Dominant

SCA-32: Cerebellar ataxia with Azospermia and Mental Impariment (ADCA I)
  Chromosome 7q32-q33; Dominant

SCA-35: Cerebellar ataxia with Upper motor neuron features (ADCA I) 53
  Protein-glutamine gamma-glutamyltransferase 6 (TGM6) ; Chromosome 20p13; Dominant

SCA-36: Cerebellar ataxia with Motor neuron involvement 54
  Nuclear Protein 56 (NOP56; NOL5A) ; Chromosome 20p13; Dominant

SCA-37: Cerebellar ataxia with abnormal Vertical Eye Movements 61
  Chromosome 1p32; Dominant

SCA-38 66
  Elongation of very long chain fatty acids-like 5 (ELOVL5) ; Chromosome 6p12.1; Dominant 66

SCA-40 67
  Coiled-coil domain-containing protein 88C (CCDC88C; Daple) ; Chromosome 14q32.11; Dominant

Dentatorubral-Pallidoluysian Atrophy (DRPLA) 48
  Atrophin-1 (DRPLA gene; ATN1) ; Chromosome 12p13.31; Dominant

Holmes ataxia Cerebelloparenchymal degeneration (CPD I)

Cerebellar vermal aplasia
Leukoencephalopathy: Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC; HLD6) 59
  Tubulin, beta-4A (TUBB4A) ; Chromosome 19p13.3; Dominant (Sporadic)


Prion disease
  Prion protein (PRNP) ; Chromosome 20p13
  Creutzfeldt-Jakob: Sporadic

Vertical and Horizontal Nystagmus
  Autosomal; Not linked to Chromosome 19

Multiple hamartoma syndrome (Cowden; Lhermitte-Duclos)
  Phosphatase & Tensin homolog (PTEN) ; Chromosome 10q23.31; Dominant

Cerebellar ataxia, Deafness & Narcolepsy (ADCA-DN) 56
  DNA methyltransferase 1 (DNMT1) ; Chromosome 19p13.2; Dominant or De novo

Cerebellar ataxia, Non-progressive with Mental retardation (CANPMR)
  Calmodulin-binding transcription activator 1 (CAMTA1) ; Chromosome 1p36.31-p36.23; Dominant

Alternating hemiplegia of childhood 1 (AHC1)
  ATPase, Na+/K+ Transporting, α2 polypeptide (ATP1A2) ; Chromosome 1q23.2; Dominant

Alternating hemiplegia of childhood 2 (AHC2)
  ATPase, Na+/K+ Transporting, α3 polypeptide 3 (ATP1A3) ; Chromosome 19q13.2; Dominant

CAPOS syndrome
  ATPase, Na+/K+ Transporting, α3 polypeptide 3 (ATP1A3) ; Chromosome 19q13.2; Dominant

Von Hippel-Lindau Syndrome
  VHL protein ; Chromosome 3p25.3; Dominant

Familial Cortical Myoclonus 58
  Nucleolar protein 3 (NOL3; ARC) ; Chromosome 16q22.1; Dominant

Myelocerebellar Disorder
  Autosomal Dominant

Hereditary ataxia with thermoanalgesia & loss of fungiform papillae

Branchial myoclonus with Spastic paraparesis & Cerebellar ataxia

Familial essential tremor
  Dominant; Chromosome 3q13

Spinocerebellar ataxia with Rigidity & Peripheral neuropathy
  Dominant Ataxia with Slow ocular saccades, Neuropathy & Orthostatism 65
  Dominant Glucose transporter 1 deficiency syndrome
  SLC2A1 ; Chromosome 1p34.2; Dominant or Sporadic Familial Dementia with Amyloid angiopathy & Spastic Ataxia
  Integral membrane protein 2B (ITM2B) ; Chromosome 13q14.2; Dominant

Episodic Ataxias


Episodic ataxias: Differential diagnosis
Type Onset
age (yrs)
Attack
duration
Symptoms Interictal features Triggers
EA1 < 20 Minutes Muscle spasms Seizures, Myokymia Exertion; Posture Δ, Stress; Startle
EA2 < 20 Hours Vertigo, Weakness Ataxia, Nystagmus Exertion; Stress; Alcohol
EA3 < 20 Minutes Vertigo, Tinnitus, Headache None Kinesigenic
EA4 20-50 Hours Vertigo, Diplopia Nystagmus, Smooth pursuit Δ
EA5 20-60 Hours Vertigo Nystagmus, Ataxia
EA6 < 10 Hours Cognitive impairment Seizures, Ataxia Fever
EA7 < 20 Hours Vertigo, Weakness None Exertion; Excitement
EA8 < 2 Mins to Hrs Ataxia, Weakness Tremor Tiredness; Stress
CSE 2 to 15 20 minutes Chorea; Ataxia; Headache Spasticity Alcohol, Fatigue, Stress, Exercise



EA 1: Episodic Ataxia / Myokymia Syndrome
  Potassium Voltage-Gated Channel (KCNA 1) ; Chromosome 12p13.32; Dominant

EA 2: Hereditary Paroxysmal Cerebellar Ataxia
  α1A Calcium channel, voltage dependent (CACNA1A) ; Chromosome 19p13.2; Dominant
Episodic ataxia 3 : With vertigo & tinnitus
  Chromosome 1q42; Dominant
Episodic ataxia 4 (EA4; PATX)
  Dominant
Episodic ataxia 5 (EA5)
  CACNB4β4 ; Chromosome 2q23.3; Dominant
EA6: Episodic ataxia + Seizures, Migraine & Alternating hemiplegia 42
  SLC1A3 (EAAT1) ; Chromosome 5p13.2; Dominant
Episodic ataxia 7 (EA7)
  Chromosome 19q13; Dominant
Episodic ataxia 8 (EA8)
  Chromosome 1p36.13-p34.3; Dominant
Episodic ataxia with paroxysmal choreoathetosis & spasticity (Dystonia-9; DYT9; CSE)
  SLC2A1 (GLUT1) ; Chromosome 1p34.2; Dominant
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References
1. Nature Genetics 1996;14:237-238
2. SCA1: Hum MolGenet 1995;4:1585-90
3. SCA2: Hum Mol Genet 1997;6:709-715
4. SCA3: Ann.Neurol. 1996;39:490-99; J.Neurol.Sci. 1995;132:71-75
5. SCA4: Am.J.Hum.Genet. 1996;59:392-399, J Neurol 2003;250:668–671, Am J Hum Genet 2005;77: Online July
6. SCA5: Nat.Genet. 1994;8:280-284
7. SCA6: Nat.Genet. 1997;15:62-69; Hum.Mol.Genet. 1997;6:1289-93; Hum.Mol.Genet. 1997;6:1283-87
8. SCA7: Am.J.Hum.Genet. 1996;59:1328-36; Nat.Genet. 1997;17:65-70
9. SCA8: Nature Genetics 1999;21:379-384
10. SCA10: Am J Hum Genet 1999;64:594-599, Nature Genetics 2000;191-194, Arch Neurol 2002;59:1285-1290, Cerebellum. 2005;4:37-42
11. SCA11: Am J Hum Genet 1999;65:420-426
12. SCA12: Nature Genet 1999;23: 391-392; Ann Neurol 2001;Nov On-Line
13. SCA13: Am J Hum Genet 2000;67:229-235, J Comp Neurol 2007;502:953-972
14. SCA14: Ann Neurol 2000;48:156-163, Arch Neurol 2002;59:1291-1295; Am J Hum Genet 2003; Online March, Neurology 2003;61:1760–1765, Ann Neurol 2005;58:720–729
15. SCA8: Neurology 2000;55:649-657, Acta Neurologica Scandinavica 2008;117:41-48
16. SCA 15: Neurology 2001;57:1913–1915, Neurobiol Disease 2003;13:147–157, Neurology 2002;58:A35, PLoS 2007; Online May
17. Neurology 2001;57:96-100, Neurology 2006;67;1236-1241
18. Hum Molec Genet 1999;8:2047-2053, Hum Molec Genet 2001;10:1441-1448, Neurology 2001;56:A130, Neurology 2003;61:1441-1443, Eur J Hum Genet 2007 Nov 28
19. Neurology 2001;56:A60
20. NEJM 2001;345:17-24
21. J Neurol 2001;248:911-914
22. Neurology 2001;57:1843–1848, Neurology 2005;64:2090–2097
23. Ann Neurol 2002;On-Line Aug, Brain 2014; Online July
24. Human Genet 2002;On-Line Sep, J Neurol 2001;248:113–120, Ann Neurology 2012; July
25. Eur Neurol 2002;48:210–217, Neuropathol Appl Neurobiol 2013 Apr 26
26. Am J Hum Genet 2003;72:191–199
27. Brain 2003;126:1293-1299, Ann Neurology 2012; July
28. Human Molecular Genetics 2003;12:1485–1496
29. Ann Neurol 2003;On-Line Aug
30. Ann Neurol 2004;55:97–104
31. Neurology 2003;61:1743–1748
32. Neurology 2004;62:17–22
33. Neurology 2004;62:327–329
34. Brain 2004;127:1172-1181
35. Lancet Neurol 2004;3:291–304, J Neurol Neurosurg Psychiatry 2014; Aug 18
36. Neurology 2004;62:1623–1625
37. Brain 2004; Online August, Am J Human Genet 2010; Online October
38. Arch Neurol 2002;59:1430-1436
39. Arch Neurol 2004;61:1242-1248
40. Neuromusc Disord 2004; Online September
41. Ann Neurol 2005;57:349–354
42. Neurology 2005; Online June 2005
43. Brain 2005; Online Oct 26
44. Nature Genetics 2006; Online Jan 22
45. Arch Neurol 2006;63:553-555
46. Arch Neurol 2004;61:257-261
47. JNNP 2008; Online November
48. Mov Disord 2009; Online June
49. Journal of Neuroscience 2009;29:9244–9254, Nature Genet 2010; Online March
50. Am J Med Genet B Neuropsychiatr Genet 2009 Aug 12
51. J Neurol 2009 Jul 31
52. Am J Hum Genet 2009; Online October, Neurology 2011;77:1853-1855
53. Brain 2010; Online November
54. Am J Human Genet 2011;89:121-130, JNNP 2014; Online December
55. PLoS Genet 2011;7:e1002325
56. Hum Mol Genet 2012 Feb 9
57. EMBO Mol Med 2012 Apr 4
58. Ann Neurol 2012;72:175–183
59. Am J Human Genetics 2013; Online April
60. Mov Disord 2013 Apr 22
61. JAMA Neurol 2013; Online April
62. NEJM 2013;369:1904-1914
63. Orphanet 2014; Online January
64. European Journal of Neurology 2014;21:607–615
65. Parkinsonism Relat Disord 2014 Apr
66. Am J Human Genet 2014; Online July
67. J Med Genet 2014 Jul 25

12/6/2014