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Spinocerebellar ataxia type 12(SCA12)

MedGen UID:
347653
Concept ID:
C1858501
Disease or Syndrome
Synonyms: SCA12; Spinocerebellar Ataxia Type12
SNOMED CT: Spinocerebellar ataxia type 12 (719208005)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): PPP2R2B (5q32)
 
Monarch Initiative: MONDO:0011439
OMIM®: 604326
Orphanet: ORPHA98762

Definition

Rare disease with manifestations of action tremor associated with relatively mild cerebellar ataxia. Associated pyramidal and extrapyramidal signs and dementia have been reported. Prevalence is unknown. Approximately 40 families have been reported. The pathogenesis seems to be related to a toxic effect at the RNA level as it is caused by a CAG expansion at the 5'' end of the PPP2R2B gene on chromosome 5q31-5q32. [from SNOMEDCT_US]

Clinical features

From HPO
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Delusion
MedGen UID:
3715
Concept ID:
C0011253
Mental or Behavioral Dysfunction
A delusion is a fixed false belief held despite evidence to the contrary. The term delusion broadly encompasses all false judgments that possess the following external characteristics to a significant, albeit unspecified, extent
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Action tremor
MedGen UID:
65875
Concept ID:
C0234376
Sign or Symptom
A tremor present when the limbs are active, either when outstretched in a certain position or throughout a voluntary movement.
Dysdiadochokinesis
MedGen UID:
115975
Concept ID:
C0234979
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to perform rapidly alternating movements, such as pronating and supinating his or her hand on the dorsum of the other hand as rapidly as possible.
Head tremor
MedGen UID:
68690
Concept ID:
C0239882
Finding
An unintentional, oscillating to-and-fro muscle movement affecting head movement.
Parkinsonian disorder
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Facial myokymia
MedGen UID:
78741
Concept ID:
C0270871
Disease or Syndrome
Facial myokymia is a fine fibrillary activity of one or more muscles innervated by the facial nerve (the seventh cranial nerve).
Progressive cerebellar ataxia
MedGen UID:
140727
Concept ID:
C0393525
Disease or Syndrome
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Sensorimotor neuropathy
MedGen UID:
207266
Concept ID:
C1112256
Disease or Syndrome
Axial dystonia
MedGen UID:
373027
Concept ID:
C1836149
Finding
A type of dystonia that affects the midline muscles, i.e., the chest, abdominal, and back muscles.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Abnormality of eye movement
MedGen UID:
99227
Concept ID:
C0497202
Finding
An abnormality in voluntary or involuntary eye movements or their control.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSpinocerebellar ataxia type 12
Follow this link to review classifications for Spinocerebellar ataxia type 12 in Orphanet.

Professional guidelines

PubMed

Mignot C, Lambert L, Pasquier L, Bienvenu T, Delahaye-Duriez A, Keren B, Lefranc J, Saunier A, Allou L, Roth V, Valduga M, Moustaïne A, Auvin S, Barrey C, Chantot-Bastaraud S, Lebrun N, Moutard ML, Nougues MC, Vermersch AI, Héron B, Pipiras E, Héron D, Olivier-Faivre L, Guéant JL, Jonveaux P, Philippe C
J Med Genet 2015 Jan;52(1):61-70. Epub 2014 Nov 19 doi: 10.1136/jmedgenet-2014-102748. PMID: 25411445

Recent clinical studies

Etiology

Ganaraja VH, Holla VV, Stezin A, Kamble N, Yadav R, Purushottam M, Jain S, Pal PK
Tremor Other Hyperkinet Mov (N Y) 2022;12:13. Epub 2022 Apr 21 doi: 10.5334/tohm.686. PMID: 35531119Free PMC Article
Aldaz CM, Hussain T
Int J Mol Sci 2020 Nov 24;21(23) doi: 10.3390/ijms21238922. PMID: 33255508Free PMC Article
Ure RJ, Dhanju S, Lang AE, Fasano A
J Neurol Neurosurg Psychiatry 2016 Nov;87(11):1191-1203. Epub 2016 Mar 16 doi: 10.1136/jnnp-2015-311693. PMID: 26985048
Li H, Ma J, Zhang X
Med Sci Monit 2014 Oct 2;20:1783-91. doi: 10.12659/MSM.891104. PMID: 25274186Free PMC Article
Brussino A, Graziano C, Giobbe D, Ferrone M, Dragone E, Arduino C, Lodi R, Tonon C, Gabellini A, Rinaldi R, Miccoli S, Grosso E, Bellati MC, Orsi L, Migone N, Brusco A
Mov Disord 2010 Jul 15;25(9):1269-73. doi: 10.1002/mds.22835. PMID: 20629122

Diagnosis

Agrawal S, Kumaran SS, Srivastava AK, Agrawal RK, Narang MK
Stud Health Technol Inform 2022 Jun 6;290:670-674. doi: 10.3233/SHTI220162. PMID: 35673101
Agarwal A, Kaur H, Agarwal A, Nehra A, Pandey S, Garg A, Faruq M, Rajan R, Shukla G, Goyal V, Srivastava AK
Parkinsonism Relat Disord 2021 Apr;85:52-56. Epub 2021 Mar 13 doi: 10.1016/j.parkreldis.2021.03.010. PMID: 33740701
Ure RJ, Dhanju S, Lang AE, Fasano A
J Neurol Neurosurg Psychiatry 2016 Nov;87(11):1191-1203. Epub 2016 Mar 16 doi: 10.1136/jnnp-2015-311693. PMID: 26985048
O'Hearn E, Holmes SE, Margolis RL
Handb Clin Neurol 2012;103:535-47. doi: 10.1016/B978-0-444-51892-7.00034-6. PMID: 21827912
Cho JW, Kim SY, Park SS, Jeon BS
Can J Neurol Sci 2008 Sep;35(4):488-90. doi: 10.1017/s0317167100009161. PMID: 18973067

Prognosis

Agarwal A, Kaur H, Agarwal A, Nehra A, Pandey S, Garg A, Faruq M, Rajan R, Shukla G, Goyal V, Srivastava AK
Parkinsonism Relat Disord 2021 Apr;85:52-56. Epub 2021 Mar 13 doi: 10.1016/j.parkreldis.2021.03.010. PMID: 33740701
Cohen RL, Margolis RL
Curr Opin Neurol 2016 Dec;29(6):735-742. doi: 10.1097/WCO.0000000000000385. PMID: 27748686
Mignot C, Lambert L, Pasquier L, Bienvenu T, Delahaye-Duriez A, Keren B, Lefranc J, Saunier A, Allou L, Roth V, Valduga M, Moustaïne A, Auvin S, Barrey C, Chantot-Bastaraud S, Lebrun N, Moutard ML, Nougues MC, Vermersch AI, Héron B, Pipiras E, Héron D, Olivier-Faivre L, Guéant JL, Jonveaux P, Philippe C
J Med Genet 2015 Jan;52(1):61-70. Epub 2014 Nov 19 doi: 10.1136/jmedgenet-2014-102748. PMID: 25411445
Li H, Ma J, Zhang X
Med Sci Monit 2014 Oct 2;20:1783-91. doi: 10.12659/MSM.891104. PMID: 25274186Free PMC Article
Swarup V, Srivastava AK, Rajeswari MR
Neurosci Res 2012 Jun;73(2):161-7. Epub 2012 Mar 16 doi: 10.1016/j.neures.2012.03.002. PMID: 22426495

Clinical prediction guides

Agarwal A, Kaur H, Agarwal A, Nehra A, Pandey S, Garg A, Faruq M, Rajan R, Shukla G, Goyal V, Srivastava AK
Parkinsonism Relat Disord 2021 Apr;85:52-56. Epub 2021 Mar 13 doi: 10.1016/j.parkreldis.2021.03.010. PMID: 33740701
Aldaz CM, Hussain T
Int J Mol Sci 2020 Nov 24;21(23) doi: 10.3390/ijms21238922. PMID: 33255508Free PMC Article
Srivastava AK, Takkar A, Garg A, Faruq M
Brain 2017 Jan;140(1):27-36. Epub 2016 Nov 17 doi: 10.1093/brain/aww269. PMID: 27864267
Cohen RL, Margolis RL
Curr Opin Neurol 2016 Dec;29(6):735-742. doi: 10.1097/WCO.0000000000000385. PMID: 27748686
Li H, Ma J, Zhang X
Med Sci Monit 2014 Oct 2;20:1783-91. doi: 10.12659/MSM.891104. PMID: 25274186Free PMC Article

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