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Spinocerebellar ataxia 50(SCA50)

MedGen UID:
1824045
Concept ID:
C5774272
Disease or Syndrome
Synonym: SCA50
 
Gene (location): NPTX1 (17q25.3)
 
Monarch Initiative: MONDO:0859334
OMIM®: 620158

Definition

Spinocerebellar ataxia-50 (SCA50) is an autosomal dominant neurologic disorder characterized by cerebellar ataxia, oculomotor apraxia and other eye movement abnormalities, and cerebellar atrophy on brain imaging. Most patients develop symptoms as adults, although childhood onset has rarely been reported. Additional more variable features may include tremor, dysarthria, dysphagia, and cognitive impairment with executive dysfunction (Coutelier et al., 2022; Schoggl et al., 2022). [from OMIM]

Clinical features

From HPO
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Apraxia
MedGen UID:
8166
Concept ID:
C0003635
Mental or Behavioral Dysfunction
A defect in the understanding of complex motor commands and in the execution of certain learned movements, i.e., deficits in the cognitive components of learned movements.
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).
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Memory impairment
MedGen UID:
68579
Concept ID:
C0233794
Mental or Behavioral Dysfunction
An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness.
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.
Postural tremor
MedGen UID:
66696
Concept ID:
C0234378
Sign or Symptom
A type of tremors that is triggered by holding a limb in a fixed position.
Head tremor
MedGen UID:
68690
Concept ID:
C0239882
Finding
An unintentional, oscillating to-and-fro muscle movement affecting head movement.
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.
Cerebellar vermis atrophy
MedGen UID:
149271
Concept ID:
C0742028
Disease or Syndrome
Wasting (atrophy) of the vermis of cerebellum.
Froment sign
MedGen UID:
713325
Concept ID:
C1290999
Sign or Symptom
An abnormal result of a physical examination of the the hand that tests for palsy of the ulnar nerve. This nerve innervates the adductor pollicis and interossei muscles and thereby enables adduction of the thumb and extension of the interphalangeal joint. An abnormal result consists in reduced functionality and muscular weakness in the pinch grip between the thumb and index finger of the affected hand as the patient attempts to pinch a piece of paper that the examiner tries to pull away. The flexor pollicis longus muscle tries to compensate for the weakness by flexing the tip of the thumb at the interphalangeal joint.
Impaired executive functioning
MedGen UID:
1617231
Concept ID:
C4544271
Mental or Behavioral Dysfunction
A disturbance of executive functioning, which is broadly defined as the set of abilities that allow for the planning, executing, monitoring, and self-correcting of goal-directed behavior while inhibiting task-irrelevant behavior. At least some degree of executive skill is needed to complete most cognitive tasks, and deficits in executive abilities are central to many clinical conditions, including fronto-temporal dementia.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Diplopia
MedGen UID:
41600
Concept ID:
C0012569
Disease or Syndrome
Diplopia is a condition in which a single object is perceived as two images, it is also known as double vision.
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.

Professional guidelines

PubMed

Mohamed Ibrahim N, Lin CH
Parkinsonism Relat Disord 2024 Dec;129:107100. Epub 2024 Aug 15 doi: 10.1016/j.parkreldis.2024.107100. PMID: 39183141
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Clin Genet 2016 Aug;90(2):105-17. Epub 2016 Jan 20 doi: 10.1111/cge.12710. PMID: 26662178

Recent clinical studies

Etiology

Wilke C, Pellerin D, Mengel D, Traschütz A, Danzi MC, Dicaire MJ, Neumann M, Lerche H, Bender B, Houlden H; RFC1 study group, Züchner S, Schöls L, Brais B, Synofzik M
Brain 2023 Oct 3;146(10):4144-4157. doi: 10.1093/brain/awad157. PMID: 37165652
Bakhtiar S, Salzmann-Manrique E, Donath H, Woelke S, Duecker RP, Fritzemeyer S, Schubert R, Huenecke S, Kieslich M, Klingebiel T, Bader P, Zielen S
Br J Haematol 2021 Sep;194(5):879-887. Epub 2021 Aug 1 doi: 10.1111/bjh.17736. PMID: 34337741
Bourassa CV, Meijer IA, Merner ND, Grewal KK, Stefanelli MG, Hodgkinson K, Ives EJ, Pryse-Phillips W, Jog M, Boycott K, Grimes DA, Goobie S, Leckey R, Dion PA, Rouleau GA
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Hall J
Cancer Lett 2005 Sep 28;227(2):105-14. Epub 2005 Jan 8 doi: 10.1016/j.canlet.2004.12.001. PMID: 16112413

Diagnosis

Mohamed Ibrahim N, Lin CH
Parkinsonism Relat Disord 2024 Dec;129:107100. Epub 2024 Aug 15 doi: 10.1016/j.parkreldis.2024.107100. PMID: 39183141
Yoon JG, Lee S, Cho J, Kim N, Kim S, Kim MJ, Kim SY, Moon J, Chae JH
Eur J Hum Genet 2024 May;32(5):584-587. Epub 2024 Feb 2 doi: 10.1038/s41431-024-01542-w. PMID: 38308084Free PMC Article
Ngo KJ, Rexach JE, Lee H, Petty LE, Perlman S, Valera JM, Deignan JL, Mao Y, Aker M, Posey JE, Jhangiani SN, Coban-Akdemir ZH, Boerwinkle E, Muzny D, Nelson AB, Hassin-Baer S, Poke G, Neas K, Geschwind MD, Grody WW, Gibbs R, Geschwind DH, Lupski JR, Below JE, Nelson SF, Fogel BL
Hum Mutat 2020 Feb;41(2):487-501. Epub 2019 Nov 25 doi: 10.1002/humu.23946. PMID: 31692161Free PMC Article
Hosking KA, Leung H, Andrews I, Sachdev R
Pediatr Neurol 2014 Mar;50(3):279-80. Epub 2013 Nov 21 doi: 10.1016/j.pediatrneurol.2013.11.011. PMID: 24368146
Martin JJ
Handb Clin Neurol 2012;103:475-91. doi: 10.1016/B978-0-444-51892-7.00030-9. PMID: 21827908

Therapy

Beyraghi-Tousi M, Sahebkar A, Houra M, Sarvghadi P, Jamialahmadi T, Bagheri R, Tavallaie S, Gumpricht E, Saberi-Karimian M
Eur J Paediatr Neurol 2024 May;50:57-63. Epub 2024 Apr 22 doi: 10.1016/j.ejpn.2024.04.009. PMID: 38669738
Shao J, Huang L, Lai W, Zou Y, Zhu Q
Molecules 2023 Jun 2;28(11) doi: 10.3390/molecules28114521. PMID: 37298997Free PMC Article
Czarny J, Andrzejewska M, Zając-Spychała O, Latos-Grażyńska E, Pastorczak A, Wypyszczak K, Szczawińska-Popłonyk A, Niewiadomska-Wojnałowicz I, Wziątek A, Marciniak-Stępak P, Dopierała M, Małdyk J, Jończyk-Potoczna K, Derwich K
Int J Mol Sci 2023 Jan 6;24(2) doi: 10.3390/ijms24021099. PMID: 36674612Free PMC Article
Diallo A, Jacobi H, Tezenas du Montcel S, Klockgether T
J Neurol 2021 Aug;268(8):2749-2756. Epub 2020 Apr 7 doi: 10.1007/s00415-020-09815-2. PMID: 32266540
Lee Y, Oh MR, Kim CH, Hwang HZ, Kim JS, Song SM, Jin DK
J Biotechnol 2002 May 23;95(3):215-23. doi: 10.1016/s0168-1656(02)00024-x. PMID: 12007862

Prognosis

Dalski A, Pauly MG, Hanssen H, Hagenah J, Hellenbroich Y, Schmidt C, Strohschehn J, Spielmann M, Zühlke C, Brüggemann N
J Neurol 2024 Sep;271(9):6289-6300. Epub 2024 Aug 2 doi: 10.1007/s00415-024-12600-0. PMID: 39095619Free PMC Article
Tan D, Wei C, Chen Z, Huang Y, Deng J, Li J, Liu Y, Bao X, Xu J, Hu Z, Wang S, Fan Y, Jiang Y, Wu Y, Wu Y, Wang S, Liu P, Zhang Y, Yang Z, Jiang Y, Zhang H, Hong D, Zhong N, Jiang H, Xiong H
Mov Disord 2023 Jul;38(7):1282-1293. Epub 2023 May 6 doi: 10.1002/mds.29412. PMID: 37148549
Alvarenga MP, Siciliani LC, Carvalho RS, Ganimi MC, Penna PS
Neurol Sci 2022 Aug;43(8):4997-5005. Epub 2022 Apr 25 doi: 10.1007/s10072-022-06084-x. PMID: 35469073
Bakhtiar S, Salzmann-Manrique E, Donath H, Woelke S, Duecker RP, Fritzemeyer S, Schubert R, Huenecke S, Kieslich M, Klingebiel T, Bader P, Zielen S
Br J Haematol 2021 Sep;194(5):879-887. Epub 2021 Aug 1 doi: 10.1111/bjh.17736. PMID: 34337741
McGrath-Morrow SA, Collaco JM, Crawford TO, Carson KA, Lefton-Greif MA, Zeitlin P, Lederman HM
J Pediatr 2010 Apr;156(4):682-4.e1. Epub 2010 Feb 20 doi: 10.1016/j.jpeds.2009.12.007. PMID: 20171651

Clinical prediction guides

Wilke C, Pellerin D, Mengel D, Traschütz A, Danzi MC, Dicaire MJ, Neumann M, Lerche H, Bender B, Houlden H; RFC1 study group, Züchner S, Schöls L, Brais B, Synofzik M
Brain 2023 Oct 3;146(10):4144-4157. doi: 10.1093/brain/awad157. PMID: 37165652
Huin V, Coarelli G, Guemy C, Boluda S, Debs R, Mochel F, Stojkovic T, Grabli D, Maisonobe T, Gaymard B, Lenglet T, Tard C, Davion JB, Sablonnière B, Monin ML, Ewenczyk C, Viala K, Charles P, Le Ber I, Reilly MM, Houlden H, Cortese A, Seilhean D, Brice A, Durr A
Brain 2022 Jun 30;145(6):2121-2132. doi: 10.1093/brain/awab449. PMID: 34927205
Ngo KJ, Rexach JE, Lee H, Petty LE, Perlman S, Valera JM, Deignan JL, Mao Y, Aker M, Posey JE, Jhangiani SN, Coban-Akdemir ZH, Boerwinkle E, Muzny D, Nelson AB, Hassin-Baer S, Poke G, Neas K, Geschwind MD, Grody WW, Gibbs R, Geschwind DH, Lupski JR, Below JE, Nelson SF, Fogel BL
Hum Mutat 2020 Feb;41(2):487-501. Epub 2019 Nov 25 doi: 10.1002/humu.23946. PMID: 31692161Free PMC Article
Klockgether T, Paulson H
Mov Disord 2011 May;26(6):1134-41. doi: 10.1002/mds.23559. PMID: 21626557Free PMC Article
Bürk K, Zühlke C, König IR, Ziegler A, Schwinger E, Globas C, Dichgans J, Hellenbroich Y
Neurology 2004 Jan 27;62(2):327-9. doi: 10.1212/01.wnl.0000103293.63340.c1. PMID: 14745083

Recent systematic reviews

de Almeida Franzoi AE, da Silva GF, de Souza Somensi E, de Moura Campos MH, Wollmann GM, Fustes OJH, Marques GL, Teive HAG
Cerebellum 2024 Dec;23(6):2593-2606. Epub 2024 Aug 29 doi: 10.1007/s12311-024-01730-w. PMID: 39198325
Diallo A, Jacobi H, Tezenas du Montcel S, Klockgether T
J Neurol 2021 Aug;268(8):2749-2756. Epub 2020 Apr 7 doi: 10.1007/s00415-020-09815-2. PMID: 32266540
de Mattos EP, Kolbe Musskopf M, Bielefeldt Leotti V, Saraiva-Pereira ML, Jardim LB
J Neurol Neurosurg Psychiatry 2019 Feb;90(2):203-210. Epub 2018 Oct 18 doi: 10.1136/jnnp-2018-319200. PMID: 30337442
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
Rossi M, Perez-Lloret S, Doldan L, Cerquetti D, Balej J, Millar Vernetti P, Hawkes H, Cammarota A, Merello M
Eur J Neurol 2014 Apr;21(4):607-15. Epub 2014 Feb 12 doi: 10.1111/ene.12350. PMID: 24765663

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