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Spinocerebellar ataxia 45(SCA45)

MedGen UID:
1622156
Concept ID:
C4540400
Disease or Syndrome
Synonyms: SCA45; SPINOCEREBELLAR ATAXIA 45
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): FAT2 (5q33.1)
 
Monarch Initiative: MONDO:0033480
OMIM®: 617769
Orphanet: ORPHA589527

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.
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.
Limb ataxia
MedGen UID:
196692
Concept ID:
C0750937
Finding
A kind of ataxia that affects movements of the extremities.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSpinocerebellar ataxia 45

Professional guidelines

PubMed

Rossi M, Hamed M, Rodríguez-Antigüedad J, Cornejo-Olivas M, Breza M, Lohmann K, Klein C, Rajalingam R, Marras C, van de Warrenburg BP
Mov Disord 2023 Mar;38(3):368-377. Epub 2022 Nov 14 doi: 10.1002/mds.29278. PMID: 36374860
van Os NJ, Roeleveld N, Weemaes CM, Jongmans MC, Janssens GO, Taylor AM, Hoogerbrugge N, Willemsen MA
Clin Genet 2016 Aug;90(2):105-17. Epub 2016 Jan 20 doi: 10.1111/cge.12710. PMID: 26662178
van de Warrenburg BP, van Gaalen J, Boesch S, Burgunder JM, Dürr A, Giunti P, Klockgether T, Mariotti C, Pandolfo M, Riess O
Eur J Neurol 2014 Apr;21(4):552-62. Epub 2014 Jan 13 doi: 10.1111/ene.12341. PMID: 24418350

Recent clinical studies

Etiology

Coarelli G, Heinzmann A, Ewenczyk C, Fischer C, Chupin M, Monin ML, Hurmic H, Calvas F, Calvas P, Goizet C, Thobois S, Anheim M, Nguyen K, Devos D, Verny C, Ricigliano VAG, Mangin JF, Brice A, Tezenas du Montcel S, Durr A
Lancet Neurol 2022 Mar;21(3):225-233. Epub 2022 Jan 18 doi: 10.1016/S1474-4422(21)00457-9. PMID: 35063116
Shimobayashi E, Kapfhammer JP
Curr Neuropharmacol 2018 Jan 30;16(2):151-159. doi: 10.2174/1570159X15666170529104000. PMID: 28554312Free PMC Article
Kuo PH, Gan SR, Wang J, Lo RY, Figueroa KP, Tomishon D, Pulst SM, Perlman S, Wilmot G, Gomez CM, Schmahmann JD, Paulson H, Shakkottai VG, Ying SH, Zesiewicz T, Bushara K, Geschwind MD, Xia G, Subramony SH, Ashizawa T, Kuo SH
Parkinsonism Relat Disord 2017 Dec;45:75-80. Epub 2017 Oct 23 doi: 10.1016/j.parkreldis.2017.10.007. PMID: 29089256Free PMC Article
van Os NJH, Jansen AFM, van Deuren M, Haraldsson A, van Driel NTM, Etzioni A, van der Flier M, Haaxma CA, Morio T, Rawat A, Schoenaker MHD, Soresina A, Taylor AMR, van de Warrenburg BPC, Weemaes CMR, Roeleveld N, Willemsen MAAP
Clin Immunol 2017 May;178:45-55. Epub 2017 Jan 24 doi: 10.1016/j.clim.2017.01.009. PMID: 28126470
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320

Diagnosis

Rossi M, Hamed M, Rodríguez-Antigüedad J, Cornejo-Olivas M, Breza M, Lohmann K, Klein C, Rajalingam R, Marras C, van de Warrenburg BP
Mov Disord 2023 Mar;38(3):368-377. Epub 2022 Nov 14 doi: 10.1002/mds.29278. PMID: 36374860
van Os NJH, Jansen AFM, van Deuren M, Haraldsson A, van Driel NTM, Etzioni A, van der Flier M, Haaxma CA, Morio T, Rawat A, Schoenaker MHD, Soresina A, Taylor AMR, van de Warrenburg BPC, Weemaes CMR, Roeleveld N, Willemsen MAAP
Clin Immunol 2017 May;178:45-55. Epub 2017 Jan 24 doi: 10.1016/j.clim.2017.01.009. PMID: 28126470
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Storey E, Gardner RJ
Handb Clin Neurol 2012;103:561-5. doi: 10.1016/B978-0-444-51892-7.00037-1. PMID: 21827915
Aralasmak A, Kocak M
Semin Roentgenol 2010 Apr;45(2):126-36. doi: 10.1053/j.ro.2009.09.009. PMID: 20171344

Therapy

Tezenas du Montcel S, Petit E, Olubajo T, Faber J, Lallemant-Dudek P, Bushara K, Perlman S, Subramony SH, Morgan D, Jackman B, Paulson HL, Öz G, Klockgether T, Durr A, Ashizawa T; READISCA Consortium Collaborators
Neurology 2023 Apr 25;100(17):e1836-e1848. Epub 2023 Feb 16 doi: 10.1212/WNL.0000000000207088. PMID: 36797067Free PMC Article
Rossi M, Hamed M, Rodríguez-Antigüedad J, Cornejo-Olivas M, Breza M, Lohmann K, Klein C, Rajalingam R, Marras C, van de Warrenburg BP
Mov Disord 2023 Mar;38(3):368-377. Epub 2022 Nov 14 doi: 10.1002/mds.29278. PMID: 36374860
Coarelli G, Heinzmann A, Ewenczyk C, Fischer C, Chupin M, Monin ML, Hurmic H, Calvas F, Calvas P, Goizet C, Thobois S, Anheim M, Nguyen K, Devos D, Verny C, Ricigliano VAG, Mangin JF, Brice A, Tezenas du Montcel S, Durr A
Lancet Neurol 2022 Mar;21(3):225-233. Epub 2022 Jan 18 doi: 10.1016/S1474-4422(21)00457-9. PMID: 35063116
Nakamura K, Yoshida K, Miyazaki D, Morita H, Ikeda S
J Neurol Sci 2009 Mar 15;278(1-2):107-11. Epub 2009 Jan 21 doi: 10.1016/j.jns.2008.12.017. PMID: 19157422
Chen X, Tang TS, Tu H, Nelson O, Pook M, Hammer R, Nukina N, Bezprozvanny I
J Neurosci 2008 Nov 26;28(48):12713-24. doi: 10.1523/JNEUROSCI.3909-08.2008. PMID: 19036964Free PMC Article

Prognosis

Saucier J, Al-Qadi M, Amor MB, Ishikawa K, Chamard-Witkowski L
J Neurol Sci 2023 Jan 15;444:120527. Epub 2022 Dec 16 doi: 10.1016/j.jns.2022.120527. PMID: 36563608
Gong Y, Chen Z, Liu M, Wan L, Wang C, Peng H, Shi Y, Peng Y, Xia K, Qiu R, Tang B, Jiang H
J Clin Neurosci 2021 Jun;88:39-46. Epub 2021 Mar 30 doi: 10.1016/j.jocn.2021.03.004. PMID: 33992201Free PMC Article
Kuo PH, Gan SR, Wang J, Lo RY, Figueroa KP, Tomishon D, Pulst SM, Perlman S, Wilmot G, Gomez CM, Schmahmann JD, Paulson H, Shakkottai VG, Ying SH, Zesiewicz T, Bushara K, Geschwind MD, Xia G, Subramony SH, Ashizawa T, Kuo SH
Parkinsonism Relat Disord 2017 Dec;45:75-80. Epub 2017 Oct 23 doi: 10.1016/j.parkreldis.2017.10.007. PMID: 29089256Free PMC Article
van Os NJH, Jansen AFM, van Deuren M, Haraldsson A, van Driel NTM, Etzioni A, van der Flier M, Haaxma CA, Morio T, Rawat A, Schoenaker MHD, Soresina A, Taylor AMR, van de Warrenburg BPC, Weemaes CMR, Roeleveld N, Willemsen MAAP
Clin Immunol 2017 May;178:45-55. Epub 2017 Jan 24 doi: 10.1016/j.clim.2017.01.009. PMID: 28126470
Radford DM, Zehnbauer BA
Surg Clin North Am 1996 Apr;76(2):205-20. doi: 10.1016/s0039-6109(05)70434-5. PMID: 8610259

Clinical prediction guides

Tamuli D, Kaur M, Jaryal AK, Srivastava AK, Deepak KK
J Clin Neurosci 2023 Jul;113:114-120. Epub 2023 May 30 doi: 10.1016/j.jocn.2023.05.019. PMID: 37257217
Saucier J, Al-Qadi M, Amor MB, Ishikawa K, Chamard-Witkowski L
J Neurol Sci 2023 Jan 15;444:120527. Epub 2022 Dec 16 doi: 10.1016/j.jns.2022.120527. PMID: 36563608
Coarelli G, Heinzmann A, Ewenczyk C, Fischer C, Chupin M, Monin ML, Hurmic H, Calvas F, Calvas P, Goizet C, Thobois S, Anheim M, Nguyen K, Devos D, Verny C, Ricigliano VAG, Mangin JF, Brice A, Tezenas du Montcel S, Durr A
Lancet Neurol 2022 Mar;21(3):225-233. Epub 2022 Jan 18 doi: 10.1016/S1474-4422(21)00457-9. PMID: 35063116
Egorova PA, Bezprozvanny IB
FEBS J 2018 Oct;285(19):3547-3565. Epub 2018 Jan 12 doi: 10.1111/febs.14366. PMID: 29253316
Kuo PH, Gan SR, Wang J, Lo RY, Figueroa KP, Tomishon D, Pulst SM, Perlman S, Wilmot G, Gomez CM, Schmahmann JD, Paulson H, Shakkottai VG, Ying SH, Zesiewicz T, Bushara K, Geschwind MD, Xia G, Subramony SH, Ashizawa T, Kuo SH
Parkinsonism Relat Disord 2017 Dec;45:75-80. Epub 2017 Oct 23 doi: 10.1016/j.parkreldis.2017.10.007. PMID: 29089256Free PMC Article

Recent systematic reviews

Rossi M, Hamed M, Rodríguez-Antigüedad J, Cornejo-Olivas M, Breza M, Lohmann K, Klein C, Rajalingam R, Marras C, van de Warrenburg BP
Mov Disord 2023 Mar;38(3):368-377. Epub 2022 Nov 14 doi: 10.1002/mds.29278. PMID: 36374860
Bayram N, Kaçar Bayram A, Daimagüler HS, Dafsari HS, Bamborschke D, Uyanik G, Erdogan M, Özsaygılı C, Pangal E, Yuvaci İ, Doğanay S, Gümüş H, Per H, Jungbluth H, Çırak S
Eur J Ophthalmol 2022 May;32(3):NP92-NP97. Epub 2021 Jun 2 doi: 10.1177/11206721211021291. PMID: 34075802
Sena LS, Dos Santos Pinheiro J, Saraiva-Pereira ML, Jardim LB
Clin Genet 2021 Mar;99(3):347-358. Epub 2020 Dec 2 doi: 10.1111/cge.13888. PMID: 33219521
van Os NJ, Roeleveld N, Weemaes CM, Jongmans MC, Janssens GO, Taylor AM, Hoogerbrugge N, Willemsen MA
Clin Genet 2016 Aug;90(2):105-17. Epub 2016 Jan 20 doi: 10.1111/cge.12710. PMID: 26662178
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320

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