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Spinocerebellar ataxia type 35(SCA35)

MedGen UID:
854733
Concept ID:
C3888031
Disease or Syndrome
Synonym: Spinocerebellar Ataxia Type35
SNOMED CT: Spinocerebellar ataxia type 35 (719300001)
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): TGM6 (20p13)
 
Monarch Initiative: MONDO:0013485
OMIM®: 613908
Orphanet: ORPHA276193

Definition

Spinocerebellar ataxia-35 (SCA35) is an autosomal dominant adult-onset neurologic disorder characterized by difficulty walking due to cerebellar ataxia. The age at onset ranges from teenage years to late adulthood, and the disorder is slowly progressive. Additional features may include hand tremor, dysarthria, hyperreflexia, and saccadic eye movements (summary by Guo et al., 2014). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400). [from OMIM]

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
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.
Pseudobulbar paralysis
MedGen UID:
10989
Concept ID:
C0033790
Disease or Syndrome
Bilateral impairment of the function of the cranial nerves 9-12, which control musculature involved in eating, swallowing, and speech. Pseudobulbar paralysis is characterized clinically by dysarthria, dysphonia, and dysphagia with bifacial paralysis, and may be accompanied by Pseudobulbar behavioral symptoms such as enforced crying and laughing.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Torticollis
MedGen UID:
11859
Concept ID:
C0040485
Sign or Symptom
Torticollis is a twisted neck as a result of shortening of sternocleidomastoid muscle. This short and fibrotic muscle pulls the head laterally and rotates the chin and face to the opposite end. Facial asymmetry may be a manifestation (summary by Engin et al., 1997).
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.
Incoordination
MedGen UID:
141714
Concept ID:
C0520966
Finding
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
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.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Impaired proprioception
MedGen UID:
346424
Concept ID:
C1856691
Finding
A loss or impairment of the sensation of the relative position of parts of the body and joint position.
Intention tremor
MedGen UID:
1642960
Concept ID:
C4551520
Sign or Symptom
A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).
Neck muscle weakness
MedGen UID:
66808
Concept ID:
C0240479
Finding
Decreased strength of the neck musculature.
Slow saccadic eye movements
MedGen UID:
232942
Concept ID:
C1321329
Finding
An abnormally slow velocity of the saccadic eye movements.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSpinocerebellar ataxia type 35

Professional guidelines

PubMed

Suppiej A, Ceccato C, Tzekov R, Cermakova I, Parmeggiani F, Bellucci G, Salvetti M, Zesiewicz T, Ristori G, Romano S
Cerebellum 2024 Dec;23(6):2226-2235. Epub 2024 Jul 8 doi: 10.1007/s12311-024-01714-w. PMID: 38976217
Domingues BMD, Nascimento FA, Meira AT, Moro A, Raskin S, Ashizawa T, Teive HAG
Cerebellum 2019 Oct;18(5):849-854. doi: 10.1007/s12311-019-01064-y. PMID: 31377949
Zhou YX, Qiao WH, Gu WH, Xie H, Tang BS, Zhou LS, Yang BX, Takiyama Y, Tsuji S, He HY, Deng CX, Goldfarb LG, Wang GX
Arch Neurol 2001 May;58(5):789-94. doi: 10.1001/archneur.58.5.789. PMID: 11346374

Recent clinical studies

Etiology

Fung JLF, Tsang MHY, Leung GKC, Yeung KS, Mak CCY, Fung CW, Chan SHS, Yu MHC, Chung BHY
Parkinsonism Relat Disord 2019 Jun;63:42-45. Epub 2019 Jan 17 doi: 10.1016/j.parkreldis.2019.01.013. PMID: 30670339
Guo YC, Lin JJ, Liao YC, Tsai PC, Lee YC, Soong BW
Neurology 2014 Oct 21;83(17):1554-61. Epub 2014 Sep 24 doi: 10.1212/WNL.0000000000000909. PMID: 25253745
Guan WJ, Wang JL, Liu YT, Ma YT, Zhou Y, Jiang H, Shen L, Guo JF, Xia K, Li JD, Tang BS
Biochem Biophys Res Commun 2013 Jan 11;430(2):780-6. Epub 2012 Dec 1 doi: 10.1016/j.bbrc.2012.11.069. PMID: 23206699

Diagnosis

Marsili L, Sharma J, Espay AJ, Migazzi A, Abdelghany E, Hill EJ, Duque KR, Hagen MC, Stephen CD, Kovacs GG, Lang AE, Hadjivassiliou M, Basso M, Kauffman MA, Sturchio A
Int J Mol Sci 2021 Jul 7;22(14) doi: 10.3390/ijms22147292. PMID: 34298918Free PMC Article
Cheng HL, Dong HL, Liu DS, Ni W, Ma Y, Yang L, Du YC, Chen DF, Dong Y, Wu ZY
Gene 2021 May 5;779:145495. Epub 2021 Feb 13 doi: 10.1016/j.gene.2021.145495. PMID: 33588035
Manini A, Bocci T, Migazzi A, Monfrini E, Ronchi D, Franco G, De Rosa A, Sartucci F, Priori A, Corti S, Comi GP, Bresolin N, Basso M, Di Fonzo A
BMC Neurol 2020 Nov 7;20(1):408. doi: 10.1186/s12883-020-01964-1. PMID: 33160304Free PMC Article

Prognosis

Manini A, Bocci T, Migazzi A, Monfrini E, Ronchi D, Franco G, De Rosa A, Sartucci F, Priori A, Corti S, Comi GP, Bresolin N, Basso M, Di Fonzo A
BMC Neurol 2020 Nov 7;20(1):408. doi: 10.1186/s12883-020-01964-1. PMID: 33160304Free PMC Article
Guo YC, Lin JJ, Liao YC, Tsai PC, Lee YC, Soong BW
Neurology 2014 Oct 21;83(17):1554-61. Epub 2014 Sep 24 doi: 10.1212/WNL.0000000000000909. PMID: 25253745

Clinical prediction guides

Manini A, Bocci T, Migazzi A, Monfrini E, Ronchi D, Franco G, De Rosa A, Sartucci F, Priori A, Corti S, Comi GP, Bresolin N, Basso M, Di Fonzo A
BMC Neurol 2020 Nov 7;20(1):408. doi: 10.1186/s12883-020-01964-1. PMID: 33160304Free PMC Article

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